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139 Cards in this Set
- Front
- Back
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Signal transduction: one cell type synthesizes a _ _ that initiates a specific response in a _ cell.
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signaling molecule
target |
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Signal transduction:signaling molecule is a _ which can be (4) and is bond by a _ molecule.
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ligand
AA acetylcholine small peptide full protein receptor |
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Target cell has a specific _ for the ligand. Responses vary, but include: cell (5)
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receptor
metabolism division (cancer) differentiation morphology, mobility |
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Reminder: nuclear receptor super family binds intracellular ligands and activates _. These receptors can be _ in which the hormone binds, goes into the _, and inhibitor is removed to regulate genes. fig 7.50 and _ in which is always located in the nucleus and is bound to DNA (HAT( _ _) and HDAC (_ _)-to inhibit gene expression) fig 7.27
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genes
homodimeric nucleus heterodimeric histone acetylase, histone deacetylase |
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Types of signaling: (4)
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endocrine
paracrine autocrine by PM attached proteins |
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Types of Signaling: Endocrine signaling: hormone is secreted into _ by endocrine gland and sent to distant target cells. fig 15.2
e.g. _ cells secreting insulin |
blood
pancreas |
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Types of Signaling: Paracrine signaling involves a _ cell that sends signal to adjacent target cell. fig 15.2 e.g. a nerve cell secretes a _.
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secretory
NT |
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Types of Signaling: autocrine signaling involves target sites that are one the _ cell. fig 15.2 e.g. secreted growth factors act back like with _ cells.
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same
cancer |
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Types of Signaling: signaling by PM-attached proteins in which signaling cell contacts adjacent target cell. fig 15.2
e.g. You can have combos: _ in paracrine and endrocrine signaling. _ _ _ (_) for PM-attached signaling and once cleaved, _ or _. |
epinephrine
EGF epidermal growth factor autocrine, paracrine |
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Examples of functional domain: EGF epidermal growth factor is a hormone that works well and is duplicated in several protiens. fig 3.11 and can be used for _ and _ signaling.
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paracrine and autocrine
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Ligand: small signaling molecule or protein: binds to receptor on _ _. Receptor changes its _ to initiate cell response. The dif receptors determine how a cell responds to _ signals and for the same ligand could initiate dif _. The same receptor in dif cells may cause dif responses depending on _ _.
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cell surface
conformation external signals responses cell type |
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Ligand: small signaling molecule or protein: e.g. acetylcholine: causes _ _ to contract, causes _ _ _ to slow its rate of contraction, causes pancreatic _ _ to rapidly secrete enzymes
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striated muscles
smooth heart muscle acinar cells |
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Ligand: small signaling molecule or protein: A particular cell response could be triggered by dif _ and _.
e.g. _ and _ both cause glycogen breakdown in liver cells also they both cause production of _ in the cytoplasm which serves as a second messenger. |
ligands, receptors
epinephrine, glucagon cAMP |
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Ligand: small signaling molecule or protein: Only apparent function of the ligands is to bind receptors to initiate _ _, _ are not used for anything else, some ligands are _ after binding to their receptors, and some receptors are degraded after binding their ligands. e.g. _-_ _
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signal transduction
ligands degraded receptor-mediated endocytosis |
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Ligand: small signaling molecule or protein: A particular cell response depends on if : _ _ that is activated, _ present in the cell that can respond to the pathway like intracellular proteins determine the _.
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signaling pathway
proteins response |
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Overview of Some Surface Receptors: (4) you need to know. e.g. 16.1
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G-protein-coupled
cytokine tyrosine kinases TGFbeta |
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Overview of Some Surface Receptors: contains various parts: (3) fig 15.3a
- residues essential to tight binding with _ which is determines by _. - residues essential to tight binding with hormone for _ _ - _ hormone receptor |
receptor
mutagenesis binding affinity growth |
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Overview of Some Surface Receptors: Growth hormone: fig 15.3a: interactions are by:
- H- and ionic bonds - _ _ _ - hydro? interactions |
h- and ionic
van der waals hydrophobic |
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Overview of Some Surface Receptors: Specific is very important in hormone:
binding specificity by the _- only one kind of ligand can bind effector specificity by _-_ _ initiates a particular cellular response. fig 15.3b Once ligand binds the two receptors can form a _ _. fig 15.3c |
receptor
receptor-ligand complex receptor dimer |
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Hormones as ligands: Lipophilic hormones
- diffuse through the _ _ - bind intracellular (_) receptors - receptor-hormone complex then acts as a _ _. e.g. _ receptor. fig 7.7 |
PM
cytosolic transcription factor glucocortocoid |
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Hormones as ligands: lipophilic hormones can bind to _ receptors and _ _ receptors
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cystolic
cell surface |
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Hormones as ligands: lipophilic hormones that bind cystolic receptors includes steroids like (6) and the steroid-receptor complex increases or decreases the _ _ of certain genes. homodimeric vs heterodimeric nuclear receptors.
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cortisol
progesterone estradiol testosterone thyroxine retinoic acid transcription rates |
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Hormones as ligands: some bind to cell surface receptors in which most are _ but some can be lipophilic or _. Receptor binds with ligands to create more _ _ inside the cell. e.g. _ _
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hydrophilic
hydrophobic second messengers cyclic AMP |
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Hormones as ligands: there are those that bind to cell surface receptors so they are hydrophilic:
- can not diffuse through _ _ 2 examples are: are growth factors - peptide hormones like (3) - small charged molecules like (2) that are mainly derived from AAs and function as hormones and NTs |
PM
insulin, growth factors (epidermal growth factor EGF and platelet derived growth factor PDGF), glucagon - epinephrine aka adrenaline which is a catecholamine and histamine for hay fever |
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Hormones as ligands: there are those that bind to cell surface receptors so they are hydrophilic, one group is small charged molecules which contain _ like epinephrine, norepinephrine, and dopamine. fig 23.19 They have very short _-_
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catecholamines
half-life |
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Hormones as ligands: there are those that bind to cell surface receptors so they are hydrophilic:
Peptide hormones and catecholamines are assoc with _ _. The cells contain a _ _ supply of peptide hormones and carcholamines which are released into the _. The lifespan of these is _. The response by target cells is also on the order of _ for catecholamines and _ for peptide hormones. |
fast response
one day blood short seconds minutes |
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Hormones as ligands: there are those that bind to cell surface receptors and are lipophilic include _ (_) which has a total of 16 and they modulate responses of other hormones in paracrine and autocrine signaling.
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prostaglandins (PDs)
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Hormones as ligands: there are those that bind to cell surface receptors and are lipophilic include prostaglandins (PDs) which participate in _ and _ responses which is inhibited by anti-inflammatory drugs like aspirin, ibuprofen, and cortisone. Other PDs affect _ _ cells like with the uterus during childbirth
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paracrine and autocrine
smooth muscle |
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__ = [R][L]/[RL] which is the measure of the _ of the _ for the ligand.
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Kd= dissociation constant
affinity receptor |
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The lower the Kd or _ _, the lower the _ conc to bind 50% of the cell-surface receptors. Overall it is equivalent to the _ constant
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dissociation constant
ligand michaelis |
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Only a fraction of _ are needed to induce the maximal physiological response.
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receptors
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Synthetic receptors:
_- mimic the function of hormones by binding to their receptors to induce a normal response _-bind to receptors, but do not activate hormone-induced responses- act as _ of the natural hormone |
agonist
antagonists |
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Binding affinity example:
Heart smooth muscle cells need high affinity ligand like (_) _ _ receptors which bind to catecholamines to increase the heart rate bind contraction force. Agonists used: _- weakest _-strongest Antagonist: _- slows heart contractions- used for cardiac arrhythmia and angina aka _ _. |
B1- adrenergic receptors
epinephrine isoproterenol alprenolol beta blockers |
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Binding Assays to Determine Kd of Agonists: For low-affinity ligands, A _ _ that measures the amount of [H3]-AP bound in increasing conc's of Isoproterenol IP and Epinephrine EP.
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competition assay
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The most important second messengers in signal transduction: (5)
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cAMP
cGMP 1,2-Diacylglycerol (DAG) Inositol 1,4,5 triphosphate (IP3) Ca2+ |
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The most important second messengers in signal transduction: Enzymes and other proteins respond to the rapid shift in second messenger conc or change _ or _ of certain proteins, leading to various effects: regulate _ _, uptake and utilization of _, and storage and mobilization of _. fig 15.9
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conformation
activity cell proliferation glucose fat |
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The most important second messengers in signal transduction: cAMP targets _ _ _ (_).
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protein kinase A
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The most important second messengers in signal transduction: cGMP targets _ _ _ (_) which opens cation channels in _cells
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protein kinase G
rod |
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1,2 Diacylglyerol DAG regulates _ _ _ with Ca2+.
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protein kinase C
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Inositol 1,4,5-triphosphate IP3 opens _ _ in ER or SR in muscle cells
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Ca2+ channels
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The maximal response of a cell to a particular ligand generally occurs at ligand conc at which most of its receptors are still _ _.
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not occupied
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Intra-cellular proteins involved in signal transduction: _-_ proteins (switch proteins) are:on when they bind (_) and off when they bind (_).
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GTP-binding
GTP GDP |
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Intra-cellular proteins involved in signal transduction: GTP-binding protein has 2 regulatory proteins:
_ _ _ (_) which helps to it to release the nucleotide and since GTP _ GDP in presence the the after the release the GDP will bind to a phosphate. _ _ _ (_) which helps to activate GTPase protein to turn GTP rapidly off again |
Guanine-nucleotide Exchange Factor (GEF)
> GTP Activating Protein (GAP) |
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Intra-cellular proteins involved in signal transduction:GTP-binding proteins: _ is one of the switch proteins used which has an intrinsic GTPase activity. Ran is in the same superfamily and also there is the _ _ proteins that interact with cell surface receptors
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Ras
Trimeric G |
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Intra-cellular proteins involved in signal transduction: GTP binding protein goes through conformational change when _ bound which allows it to interact with _ proteins that it regulates. fig 15.8 when it hydrolyzes to _ it opens
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GTP
effector GDP |
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Intra-cellular proteins involved in signal transduction: Protein Kinases which put _ on proteins. _ take phosphates off again. Kinases are more _ and more _.
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phosphates
phosphotases regulated specific |
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Intra-cellular proteins involved in signal transduction: Protein Kinases: 3 main types of phosphorylation: (3) where phosphate is put on _ group, etc
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tyrosine
serine/threonine hydroxyl group |
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Intra-cellular proteins involved in signal transduction: Protein kinases are regulated by a _ or by their own _ or by direct contact with other proteins or by the conc of various _ _ like cAMP and Ca2+.
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receptor
phosphorylation second messengers |
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Intra-cellular proteins involved in signal transduction: Adapter Proteins: cannot do anything _ so they act as a _ or a link bn other proteins (receptor and signaling)
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alone
bridge |
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Intra-cellular proteins involved in signal transduction: Adapter Proteins do not have _ enzyme activity but instead have docking sites for _ proteins. These sites include _ _ # (SH2), _ _ # (SH3), and _-_ _ (PTB) domains.
_ and _ bind phosphyotyrosine. _ binds proline-rich sequences. |
intrinsic
effector src homology (SH2), src homology (SH3), Phospho-Tyrosine Binding (PTB) SH2 and PTB SH3 |
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Intra-cellular proteins involved in signal transduction: G Protein Coupled Receptors (GPCRs) called _-_ _ in which the amino terminus likes _ the cell and the carboxy terminus lies _ the cell.
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seven-pass receptors
outside inside |
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Intra-cellular proteins involved in signal transduction: G Protein Coupled Receptors (GPCRs): When bound to a ligand it goes through a _ _ on the inside of the cell and a specific region reacts with the _ protein
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conformation change
G |
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Transduction Mechanism of G Protein Coupled Receptors (GPCRs): G protein is bound to 3 subunits: (3)
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alpha
beta gamma |
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Transduction Mechanism of G Protein Coupled Receptors (GPCRs): G beta and G gamma always form a _.
1. receptor binds with _ and goes through conformation change. 2. receptor then binds with _ _ subunit 3. binding induces conformational change in G beta gamma and _ dissociates and is replace by _ 4. The ligand leaves the receptor and G beta gamma binds with _ to activate it. 5. Hydrolyzes _ to _ and causes G alpha to dissociate from effector and combine with _ _ _. ** NOTE that alpha and gamma are _ so they are covalently linked to HC group with puts them in PM.** |
dimer
1. ligand or hormone 2. beta gamma 3. GDP, GTP 4. effector 5. GTP, GDP; G beta gamma prenylated |
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Transduction Mechanism of G Protein Coupled Receptors (GPCRs): G alpha is activated for a _ _ but activated _ protein and in the end the inactive _ _ protein complex is reassembled.
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short time
effector trimeric G |
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G Protein Coupled Receptors (GPCRs): large family of receptors: e.g. (4) which all bind to G proteins at the _ subunit.
e.g. epinephrine is produced by _ _ aka adrenaline is released in times of fright or heavy exercise. _ is needed quickly and provided by hydrolysis of _. |
light-activated rhodopsin
oderant hormones NTs alpha adrenal glands glucose glycogen |
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Major Classes of Trimeric G Proteins and their effectors: table 15.1: Galpha-s: stimulates _ _ effector by _ , the secondary messenger which is increased. e.g. _-_ receptor
Galpha-i inhibits _ _ effector that produces cAMP which is _ to change membrane potential. e.g. _-_ receptor |
adenylyl cyclase
cAMP beta-adrenergic adenylyl cyclase decreased alpha2-adrenergic |
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(FRET) _ _ _ _
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Fluorescence Resonance Energy Transfer
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Fluorescence Resonance Energy Transfer (FRET): used to demonstrate association and dissociation of _ in living cells.
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proteins
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Fluorescence Resonance Energy Transfer (FRET): In an amoeba, cAMP is used as an _-_ _. Put yellow Fluorescence on G beta-gamma and cyan fluorescence on G alpha subunit, then a laser light can activate only the _ colored protein. If these two are not interacting with each other, then you'll see the light emitted by the _ protein but if these two are close then the wavelength released from _ _ subunit stiumulates the yellow on the _ _ _ subunit.
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extra-cellular ligand
cyan cyan g alpha g beta gamma |
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Fluorescence Resonance Energy Transfer (FRET): If done in the absence of cAMP then you see you get _ fluorescence and if you add cAMP you get _ fluorescence bc the subunits have separated to the G alpha cant transfer a photon via _ to G beta gamma. fig 15.14a
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yellow
cyan resonance |
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Chimeric receptors were made to define functions of _ _. loop _ connecting H5 and H6 interacts with trimeric G, determines _ for either Galpha-i or Galpha-s. fig 15.12
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individual domains
specificity |
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Epinephrine aka adrenaline binds:
1. beta-adrenergic receptors on heptacytes and adipose cells release _ and _ _ for quick energy (ATP) production. e.g. _ _ cells 2. Beta-adrenergic receptors on heart muscle cells to increase _ rates and _ and to better transport _ and _ to the muscle cells 3. beta-adrenergic receptors on smooth muscle cells of intestines; cause them to _ and to briefly shut down _ function. 4. alpha2 adrenergic receptors in smooth muscles lining blood vessels of the _, _, and _ to constrict vessels to cut off blood flow to shunt blood to skeletal muscles, heart, and brain |
1. glucose, FAs, striated muscle
2. contraction, force, oxygen, nutrients 3. relax, digestive 4. skin, intestine, kidney |
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Epinephrine aka adrenaline binds: _ and _ receptors to activate G alpha-s which then activates _ _...all to elevate level of _
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beta1 and beta2
adenylyl cyclase cAMP |
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Epinephrine aka adrenaline: on the other hand, it binds _ and _ receptors to activate G alpha-i which then inhibits _ _...all to decrease level of _.
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alpha1 and alpha2
adenylyl cyclase cAMP |
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Epinephrine aka adrenaline: alpha 1 and beta 1 etc will not be on the same cell bc
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they have conflicting activities
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Fig 15.21: Thus adenylyl cyclase and the production of cAMP are under _ and _ control. Remember _ is a powerful secondary messenger.
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positive and negative
cAMP |
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Fig 15.21: Hormone induced activation of adenylyl cyclase in adipose cells: which have _-_ GPCRs but not _-_ GPCRs. Hormone (3) stimulates _ _ to make cAMP
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beta-adrenergic
alpha-adrenergic epinephrine, glucagon, ACTH adenylyl cyclase |
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Fig 15.21: Hormone induced inhibition of adenylyl cyclase in adipose cells: _ _-_ is activated and hormone (2) is released which stops the production of _ by adenylyl cyclase
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G alpha-i
PGE1 and Adenosine cAMP |
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A generic adenylyl cyclase has: fig 15.22a
- converts _ to _ - # catalytic domains - # transmembrane domains with # helices each |
ATP to cAMP
2 2 |
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cAMP is a secondary messenger:
- activates _-_ _ _ (_) aka Protein Kinase A (PKAs) which is a _/_ kinase that phosphorylates target proteins - has 2 _ subunits and 2 _ subunits which makes a _ (inactive). To activate, _ binds the regulatory subunit causes catalytic subunits to _ from regulatory. |
cAMP-dependent protein kinases (cAPKs)
serine/threonine regulatory, catalytic, tetramer cAMP, dissociate |
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cAMP is a secondary messenger: each _ subunit binds 2 cAMPs to each: first binding drops the _ for the second binding aka _. fig 15.23
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Regulatory
Kd cooperativity |
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The Synthesis of Glycogen in Liver and Muscle: fig 15.24: _ _ will combine UDP-glucose and Glycogen
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glycogen synthase
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Glycogenolysis: classic regulatory pathway involving cAMP: _ _ splits off one glucose residue at a time as glucose 1-phosphate
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glycogen phosphorylase
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Glycogenolysis: classic regulatory pathway involving cAMP:
-in muscles, glucose 1-phosphate is made into _ #-_ which feeds into glycolysis to make _. -in liver cells, glucose 1-phosphate is converted into _ _ which is released into the blood for _ and _. fig 15.24 |
glucose 6-phosphate
ATP free glucose muscle and brain |
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FIGHT OR FLIGHT RESPONSE:
Epinephrine + _ _ receptor (_) + G alpha-s + adenylyl cyclase increase the cAMP levels which activates _-_ _ _ (_) which phosphorylates _ _ _ (_) which phosphorylates _ _ (_) and now it is activated for glycogen breakdown to make ATP. cAMP-dependent Protein Kinase (PKA) also phosphorylates _ _ which makes it inhibit glycogen synthesis. fig 15.25 slide 55 |
beta adrenergic (GPCR)
cAMP-dependent Protein Kinase (PKA) Glycogen Phosphorylase Kinase (GPK) Glycogen Phosphorylase (GP) glycogen synthase |
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FIGHT OR FLIGHT RESPONSE:
When no stimulus is present aka cAMP is low... glycogen phosphorylase kinase (GPK) and glycogen phosphorylase (GP) are inhibited by _ _ # and it activates _ _ which activates glycogen synthesis. fig 15. 25 slide 56 |
phosphoprotein phosphatase I
glycogen synthase |
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FIGHT OR FLIGHT RESPONSE:When stimulated by epinephrine,
cAMP levels increase which activates cAMP-dependent protein kinase (PKA) which phosphorylates (GPK) and (GP) and it is activated for glycogen breakdown to make ATP. PKA also does a _ _ to desensitize the beta adrenergic receptor (GPCR) and activates _ _ _ to inhibit phosphoprotein inhibitor protein fig 15.25 slide 57 |
feedback suppression
phosphatase inhibitor protein |
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Bacterial Toxins that affect GPCR pathway via G alpha: Cholera toxin (Vibrio cholerae)
- _ modification of G alpha-s - G alpha-s-GTP locked in _ state - _ _ remains active so _ levels remain elevated. Results in: massive _ _ into intestines aka diarrhea and _ of tissues, lethal if not treated. Caught by drinking contaminanted water |
covalent
active adenylyl cyclase cAMP water flow dehydration |
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Bacterial Toxins that affect GPCR pathway via G alpha: Cholera toxin or (_-_) activates G alpha-s so _ of GTP cannot occur
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ADP-ribosylation
GTP |
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Bacterial Toxins that affect GPCR pathway via G alpha: Pertussis Toxin (Bordetella pertussis)
- G alpha-i works with _ _ receptors to block adenylyl cyclase activity - s1 subunit of toxin ADP-ribosylates the _. - G alpha-i is locked into an _ state so adenylyl cyclase can not be inhibited causing the _ _. |
alpha adrenergic
G alpha-i inactive whopping cough |
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Bacterial Toxins that affect GPCR pathway via G alpha: With each step there can be _ to give a stronger response. fig 15.26
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amplification
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Three Events that Turn Off Signal Transduction for GPCRs:
1. binding of GTP to the alpha subunit _ the Kd for the interaction bn the receptor and ligand so ligand easily _. 2. GTP bound to alpha subunit hydrolyzes to _. 3. cAMP degrades quickly by _ _ (_) and _ which keeps it under complex regulation |
increases, readily
GDP cAMP phosphodiesterase (PDE), Ca2+ |
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Event that Turn Off Signal Transduction for GPCRs: Receptors can be desensitized by _.
- e.g. _ receptor - if receptor is constantly exposed to epinephrine for _ _ of time, it will still bind to epinephrine but _ transduce the signal - _ feedback - specifically, constantly high levels of _ lead to _ phosphorylation of epinephrine receptor aka _ _. |
phosphorylation
prolonged period, won't negative cAMP PKA heterologous desensitization |
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Events that Turn Off Signal Transduction for GPCRs:
- _ _- only activated beta-adrenergic receptors are phosphorylated by a _-_ _ _ (_) - once the receptor is highly phosphorylated, _-_ binds to block its activation of G alpha-s and also facilitates formation of _-_ _ for endocytosis of the bound receptor |
homologous desensitization
beta-adrenergic receptor kinase (BARK) Beta-arrestin clathrin-coated vesicles |
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Events that Turn Off Signal Transduction for GPCRs: Degree of receptor phosphorylation is an _ measure of [ligand] and as ligand increases then phosphorylation _ and desensitization _.
But receptors are constantly being dephosphorylated by _ thus re-sensitized |
indirect
increases increases phosphatases |
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Once GPCRs are heavily phosphorylated by BARK which provides a binding site for _-_ which binds to phosphorylated residues on GPCR and interacts with _ and (_) to start endocytosis of receptor. fig 15.27
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beta-arrestin
clathrin, AP2 |
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cAMP has dif effects in different cell types:
Liver and Skeletal muscle activate _ which leads to glycogen breakdown beginning with hormone (_) |
cAMP
epinephrine |
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So PKAs are localized:
In heart muscle, there is a kinase-associated protein (_) localized to the outer nuclear envelope. To drop cAMP levels, _ _ (_) is activated. There is a _ feedback loop for tightly regulated control of local cAMP conc. fig 15.28 |
AKAP
PDE= cAMP Phosphodiesterase negative |
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G Protein-Activated Adenylyl Cyclases to G Protein-Activated Ion Channels:
1. Cells maintain voltage across PM, so _ is high in cell and _ is high outside of cell. _ charge inside the cell 2 ion channels open and close to change PM _. e.g. K+ diffuses _ and Na+ diffuses in. 3. some of these channels are NT receptors. e.g. 3 |
1 K+, Na+, negative
2 potential, out, in 3 glutamate, serotonin, nicotinic acetylcholine in nerve-muscle synapses |
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G Protein-Activated Adenylyl Cyclases to G Protein-Activated Ion Channels:
4. some NT receptors are GPCR that interact with _ _ _ to regulate ion channel. e.g. _ _ _ receptors 5. some GPCRs indirectly regulate ion channels via _ _. e.g. _ receptors and _receptors |
4trimeric G Protein
cardiac muscarinic acetylcholine 5 second messengers, odorant, photo |
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Acetylcholine receptors:
acetylcholine has dif effects on striated muscle VS heart muscle - causes striated muscle to _ by _ _ receptors - causes heart muscle cells to _ _ rates where acetylcholine binds to _ _ receptors on cells and creates a release of _ by G alpha-i which causes the _ _ _ subunit from cell which causes a sustained _ of membrane and contraction _. fig 15.15 |
contract
nicotinic acetylcholine slow contraction muscarinic acetylcholine K+ G beta gamma hyperpolarization decline |
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Rod cells for night vision or in low light, they are more sensitive aka _ _. fig 15.16 The membranes have a GCPR called _ which is activated by light and consists of _= a 7-pass membrane protein and is coupled with _-_-_ which is light sensitive.
_ is the trimeric G protein coupled to rhodopsin found only in rod cells then G alpha-t indirectly regulates _-_ _ channels. _ is the secondary messenger. Changes from cis to trans conformation upon _ _ and now transducin is activated. fig 15.17 |
visual adaptation
rhodopsin opsin 11-cis-retinal transducin cGMP-gated cation cGMP photon absorption |
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Rod cells for night vision:
1. _ absorbs photon and becomes activated 2. Then G alpha-t becomes activated and release from _ _ _ which then it activates a cGMP _. 3. When cGMP is present it opens _-_ ion channel that allows _ and _ to leak into the cell 4. membrane is partially _. Low light levels cause channel to _ so membrane fully polarizes and _ release is blocked and brain perceives this as light. fig 15.18 Activation of pathway _ the second messenger and NT _ signal which is intrepreted as light. |
1. rhodopsin
2. G beta gamma, phosphodiesterase 3. cGMP-gated, Na+, Ca2+ 4. depolarized close NT destroys blocks |
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Low light level causes channels to close:
1. activated transducin activates _ _ (_). 2. Transducin binds the 2 inhibitory _ subunits of PDE 3. alpha and beta subunits convert _ to _ and channels close 4. membrane becomes more _ and NT release is _. 5. Brian perceives this as _. |
cGMP phosphodiesterase (PDE)
gamma cGMP to GMP polarized blocked light |
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Turning off rod cells signal:
After activation, _ dissociates from trans-retinal terminating signal. Free trans-retinal converts back to _-form Transducin is active for a fraction of a second: - a specific _ _ _(_) deactivates transducin - _ _ is rapidly deactivated - _ rises again to re-open channels |
opsin
cis GTPase accelerating protein (GAP) cGMP phosphodiesterase cGMP |
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Deactivation of rod cells in bright light:
- triggered by _ _ and related to _-_ _ _ (_) - phosphorylated _ (activated) is slow to activate transucin - the more _, the more phosphorylation opsin receives - _-_ finally binds to block all transducin activation fig 15.20 |
rhodopsin kinase, beta-adrenergic receptor kinase, (BARK)
opsin light beta-arrestin |
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When rod cell is shut down, Transducin components of _ and _ move away from the _ _ (_) which is just another level of regulation
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G alpha
G beta gamma outer segments (OS) |
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PKA activation:
Ligand to GPCR to _ _-_-_/ _ _ _ which seperates and level of cAMP _ |
G alpha-s-GDP/G beta gamma
increases |
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PKA deactivation:
Ligand to GPCR to _ _-_-_/ _ _ _ which seperates and level of cAMP _ and G beta gamma activates _ _ |
G alpha-i-GDP/G beta gamma
decreases ion channel |
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Rod cells activation:
Photon to GPCR to _ _-_-_/ _ _ _ which seperates and level of _ _ and activates _ _. |
G alpha-t-GDP/G beta gamma
cGMP decreases ion channel |
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Phosphatidylinositol (PI) as a second messenger: _ and _ are powerful second messengers. Activation of _ _ (_) is via hormone binding to G Protein-coupled receptors and activation of G alpha-o and G alpha-q. fig 15.29
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IP3 and DAG
phospholipase CBeta (PLCB) |
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Inositol 1,4,5-triphosphate (IP3) is free to diffuse into the _.
It releases _ as a second messenger - in cytosol, level is _ - pumps constantly move free Ca2+ into mitochondria, ER, vescicles, and out the cell - release of it into cell is used to _. |
cytoplasm
Ca2+ low tranduce |
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IP3/DAG pathway and elevation of cytosolic Ca2+:
1. ligand binds GPCRs to activate _ _-_ or _ _-_ leading to activation of _ _. 2. PIP3 is cleaved by phospholipase C to get _ and _. 3. IP3 diffuses through _ and opens _ _of ER which causes a rise in Ca2+ in cytosol 4. _ _ _ (PKC) is recruited to PM where it is activated by DAG 5. The activated PKC phosphorylates _ and _ to alter their activity 6. When Ca2+ levels are depleted, a protein opens channel for _ of Ca2+ into cell. fig 15.30 |
1. G alpha-o, G alpha-q, phospholipase C
2 IP3 and DAG 3 cytoplasm, Ca2+ channels 4 Protein Kinase C 5 enzymes and receptors 6 influx |
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To turn off signaling:
- Ca2+ depleted from the _ by the pumps in ER and PM - _ is quickly converted to _ which is useless on the channels - dif cells have dif responses to IP3 due to: dif amts of Ca2+ in the _ and dif _ of Ca2+ channels - Once Ca2+ rises in cytosol, it acts as a _ _ to: trigger insulin release in pancreatic B cells, help induce contraction of _ and _ muscles, facilitate _ of glycogen to glucose 1-phosphate in muscle and liver cells NOT activated by _, activate calmodulin, and help activate PKC. |
cytosol
IP3 to IP2 ER, isoforms smooth and striated muscles lysis, epinephrine |
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To turn off signaling: Rise of Ca2+ in cytosol that activate calmodulin which is _ (in all cells), each molecule binds to # Ca2+ ions, and binding is _. It is a regulatory _ _ on some myosin motors and activates Myosin Light Chain Kinase (MLCK) on myosin #.
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ubiquitious
4 cooperative light chain II |
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To turn off signaling: Rise of Ca2+ in cytosol that activate calmodulin:
Ca2+ + DAG uses _ _ _ (_) to begin glycogen synthase When there is increased levels of cAMP then _ protein is triggered to lower levels of cAMP |
protein kinase C
phosphodiesterase |
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To turn off signaling: Rise of Ca2+ in cytosol that activate calmodulin:
Ca2+-Calmodulin acts as a co-factor for: 1. _ _ where it degrades cAMP to 5'-AMP to terminate cAMP as a second messenger 2. _ _ _ (_) where it has alpha-beta-gamma-delta subunits, gamma is catalytic, alpha and beta are regulatory and delta is _ 3. several protein _ also where substrates are transcription factors 4. _ _ (NO) _ where cGMP is a secondary messenger and is made by _ _ in two forms: receptor-activated form and nitric oxide (NO)-activated form |
1 cAMP phosphodiesterase
2 glycogen phosphorylase kinase (GPK), calmodulin 3. kinases 4. nitric oxide synthase, guanylate cyclase |
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To turn off signaling: Rise of Ca2+ in cytosol that activate calmodulin as a co-factor for Nitric Oxide (NO) synthase:
e.g. Relaxation of arterial smooth muscle by NO and cGMP 1. NO is synthesized by the presence of _ and elevation of _ level 2. NO diffuses through tissues and activates NO receptor with _ _ activity in nearby smooth muscle 3 there is a rise in _ which activates protein kinase G 4 The muscle then _ and blood vessel _ occurs |
1 acetylcholine, Ca2+
2 guanylyl cyclase 3 cGMP 4 relaxes, dilation |
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Diacylglycerol (DAG) is a second messenger:
- activates a family of _ _ _ - before hormone stimulation, (_) is soluble in cytosol - rise in Ca2+ causes PKC to bind to inner leaflet of _ _ - once at membrane, PKC is fully activated by (_) - thus, both _ and _ are needed for PKC activation - activated PKC inactives _ _ and regulates _ _ |
protein kinase C
PKC Plasma Membrane DAG Ca2+ and DAG glycogen synthase transcription factors |
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Ligand to GPCR to G alpha-o-GDP/beta gamma (same with G alpha-q) the subuntis seperate then activate _ _ _ (_) which makes the secondary messengers (_) and (_) and after an increase in Ca2+ level two things can happen:
1. _ _ _ (_) is activated to phosphorylate 2. DAG activates calmodulin which does 2 things: 1promotes _ _ to mediated by seconday messenger (_) increase 2 activates _ _ or regulating _ _. |
phospholipase C (PLC)
IP3 and DAG protein kinase C (PKC) Nitrogen synthase cGMP protein kinases and cAMP phosphodiesterase |
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GPCRs and Phosphatidylinositol Signal Transduction and Gene Expression:
1 Phospholipase makes _ and _ 2 It also activates the transcription factor (_) which goes into the nucleus and transcribes DNA from genes involved in regulating _ _. |
IP3 and DAG
Tubby eating behavior |
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fig 16.31 CREB = cAMP response element binding protein which is phosphorylated in _ to help assemble transcription complex so it is a _-_
The genes have _ _ _ (_) |
nucleus
co-activator CREB Response Elements (CREs) |
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ACTH
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adrenocorticotropic hormone- for cell signalling
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GTPase super family
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Guanine Nucleotide Binding proteins
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GAP
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Guanine activating protein
GTP to GDP |
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GEF
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guanine exchange factor
GDP to GTP |
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_ _ _ in heart muscle to activate G protein to open K+ channels to flow out of cell= hyperpolarization= lower muscle contraction
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muscarinic acetylcholine receptor
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rhodopsin has opsin which contains _ with light-absorbing _-_-_
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GPCR
11-cis-retinal |
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G protein for rhodopsin is _
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tranducin
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light absorption by rhodopsin induces activation of _ _
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cGMP phosphodiesterase
to change cGMP to 5'-GMP |
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_ _ is activated by phosphorylation of opsin
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rhodopsin kinase
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_-_ binds with rod cells to increase light desensitization
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Beta-arrestin
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negative feedback by rod cell by _ _ and _-_
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rhodopsin knase
beta-arrestin |
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AC effector with secondary messenger (_)
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adenylyl cyclase
cAMP |
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_ _ _ (_) mediates effects of cAMP- adds it to turn on
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protein kinase A (PKA)
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glycogen to glucose 1-phosphate by _ _
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glycogen phosphorylase
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_ _ _ activates and phosphorylates glycogen phosphorylase
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glycogen phosphorylase kinase
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_ _ mediates lowering cAMP and inactivating PKA
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phosphoprotein phosphatase
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BARK
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beta adrenergic receptor kinase
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AKAP- restrict cAMP responses
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A kinase-associated protein
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phospholipase C uses secondary messengers _ and_
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IP3 and DAG
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DAG
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1,2 Diacylglycerol- in membrane
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IP3
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inositol 1,4,5-triphosphate-diffuse freely
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DAG activates _ _ _ for cell gowth and metabolism
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protein kinase C
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_ receptor binds to acetylcholine and activates phospholipase C
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Go
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NO Synthase is mediated by _
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cGMP
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_ opens Ca2+ channels in ER to increase Ca2+
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IP3
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Ca2+ and calmodulin regulate _ _
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cAMP phosphodiesterase
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