Biochem 442 Exam 1

Front 1

Plasma Membrane

Back 1

Lipid bilayer: Center with hydrophobic tails, hydrophilic heads on either side.

Front 2

Nucleus

Back 2

Contains DNA, site of RNA synthesis and processing

Front 3

cytoplasm

Back 3

site of protein synthesis and energy metabolism

Front 4

Organelles

Back 4

specific sites with specific functions contained in the cell

Front 5

Endoplasmic Reticulum

Back 5

Protein Synthesis and secretion

Front 6

Mitochondria

Back 6

Generation of ATP

Front 7

Golgi

Back 7

Protein sorting

Front 8

Endosomes, lysosomes,peroxisomes

Back 8

Names are indicative of functions as organelles. Endosomes endocytose vesicles. Lysosomes create an environment for protein/organic compound degradation. Peroxisomes reduce/oxidize.

Front 9

eIF-2 (translational control)

Back 9

Major regulator in protein synthesis. Guides small ribosomal subunit with Met attatched to the start site. Must hydrolyze GTP bound in order to detach and allow for large ribosomal subunit attachment.

Front 10

Regulation of eIF2 (guanine nucleotide exchange factor only) (translational control)

Back 10

eIF2 bound with GDP is inactive, eIF2B binds eIF2 and releases the bound GDP and attaches GTP, releasing a new active eIF2.

Front 11

Regulation of eIF2 (guanine nucleotide exhange factor and phosphorylation) (translational control)

Back 11

in absence of active eIF2B, excess eIF2 remains in inactive state with GDP bound. Protein kinase can phosphorylate inactive GDP bound eIF2B and lock it into inactivity even in eIF2B binds.

Front 12

RNA stability: POLY A- Tails (translational control)

Back 12

Poly-A tail is gradually shortened. This could caused decapping followed by rapid 5' to 3' degradation, or if the cap is kept 3' to 5' degradation.

Front 13

RNA Stability: Instability sequence (translational control)

Back 13

Instability sequence cause endonuclease to cleave that portion of the RNA; if poly A tail endonucleased then rapid degradation.

Front 14

Iron Transport (translational control)

Back 14

Components:
Iron
Transferrin - carries iron through blood stream
TFR- binds to transferrin on outside of cells, causes iron to be imported
Ferritin- iron storage protein inside cells
Aconitase- binds RNA structures on ferritin (not translated) and TFR (translated, blocking instability sequence) in absence of iron.

Front 15

Iron transport (translational control) Pt. 2

Back 15

Aconitase will bind to ferritin RNA (before protein sequence) and TFR RNA (after protein sequence if iron concentration drops. TFR Stabalized and translated, ferritin is blocked from translation. With high iron concentrations, aconitase will not bind to either, ferritin is translated (storing iron), instability sequence on TFR RNA showing causes degradation.

Front 16

miRNAs (translational control)

Back 16

Can be used in RISC (RNA induced silencing complex). With extensive match, the mRNA is sliced and rapid degradation by RISC (argonaute w/ other proteins) Less extensive matches (seed) can cause inhibition of translation and activate deadenylation.

Front 17

miRNAs (translational control) pt. 2

Back 17

Can target multiple mRNAs, can work combinatorially, can be cell type specific.

*Antagomirs bind to miRNA with high affinity, releasing them from mRNA.

Front 18

IRES (translational control) (Polio)

Back 18

*Polio virus brings in enzymes to cleave eIF4G, making it non function. Polio virus RNA can bind ribosomes and cleaved eIF4G via IRES.

Internal Ribosome Entry Sites allow for the translation of mRNA even without full initiation complexes for ribosomes.

Front 19

Moving proteins across membranes (Protein trafficking)

Back 19

1)Ribosome translation into membrane of ER or inside ER.
2) Vesicle budding from donor compartment then fusion to target compartment.

Front 20

Topology (Protein trafficking)

Back 20

All proteins that are inside a vesicle will fuse in a way where they remain inside the target compartment. If going outside of cell, proteins will be released out of cell.

Front 21

Budding and Fusion (protein trafficking)

Back 21

Coat proteins facilitate the budding of vesicles. Coated vesicles lose their coat before moving towards target compartments and fusion of membranes.

Front 22

Clathrin (protein trafficking)

Back 22

coats vesicles from extracellular space to the inside and also from the golgi apparattus towards extra cellular space.

Front 23

COPI (protein trafficking)

Back 23

coats from Golgi to ER.

and from GOLGI to Extracellular space.

Front 24

COPII (prot. trafficking)

Back 24

coats from ER to golgi.

Front 25

Clathrin (protein trafficking) molecular structure

Back 25

three heavy chains and three light chains tethered to each other at a center. Heavy chains bind adaptins. Adaptins bind to receptor proteins on cell membrane.

Front 26

Adaptins(protein trafficking)

Back 26

Help in clathrin coating of cell membranes in order to make and bud the membrane.

Front 27

Phosphoinositides (protein trafficking)

Back 27

Initiation of vesicle assembly

Front 28

Arf protein (protein trafficking)

Back 28

Arf protein helps to form vesicles by recruiting coat proteins. Arf is bound to GDP in the inactive state. In the active state, it is bound to GTP and swings down a myristoyl fat tether arm into a lipid membrane. After GTP is hydrolyzed, arm swings back, and Arf falls off.

Front 29

GEF (protein trafficking)

Back 29

Regulates amount of active ARF. Guanine nucleotide exchange factor. Replaces GDP bound to Arf with GTP.

Front 30

GAP (protein trafficking)

Back 30

Regulates amount of inactive Arf. HYdrolyzes the GTP on active Arf to turn it into GDP. Turns active to inactive.

Front 31

Rabs (protein trafficking)

Back 31

Proteins that play a key role in localizing proteins to certain locations. rabs on vesicle membranes recognize rab effectors on membranes in order to tether and dock the vesicle to the membrane. This allows for trans-snare complex to form and fuse the vesicle. v-snare (vesicle) to t-snare (membrane). Rab-GTP active, GDP inactive. Need GEF. - PRENYLATED

Front 32

Botullinum Toxin

Back 32

Botox cleaves either the v or t snares between vesicles carrying neurotransmitters that are docked onto the synaptic membrane of the neuron. this prevents the release of neurotransmitters from the neuron to the muscle cell. Lack of muscle contraction.

Front 33

Tetanus

Back 33

Works like botox, except on inhibitory neurons. Constant muscle contraction.

Front 34

vesicle cargo

Back 34

Can be non selective or selective. Non selective, anything in vesicle formation area will be inside vesicle. Selective: specific receptors for specific cargo or certain membrane bound proteins.

Front 35

LDL receptors

Back 35

LDL receptors bind low density lipoprotein. Once they bind LDL (cholesterol + protein) they bind clathrin on the clathrin binding region (inside of cell) and vesicles form into the cell.

Front 36

LDL mutants

Back 36

No receptor. No clathrin binding region. No LDL binding region.

Front 37

Signal Sequences

Back 37

Organizes where the protein should be. Can be contained in different locations of the protein.

no signal sequence: cytosolic

KDEL: Lys-Asp-Glu-Ile return to ER

Hydrophobic sequences (5-7): import into ER

Rich in Leu/Ile: export from nucleus

Rich in + charges (Lys/Arg): import into nucleus

Front 38

Chaperones (hsp70 & hsp60-like protein)

Back 38

Chaperones aid in the folding of proteins that have hydrophobic domains.

Front 39

HSP70

Back 39

HSP-70 binds onto these domains with ATP bound. ATP is hydrolyzed after binding to these regions. Once there is an Adenosyl transferase (ADP swapped with ATP) action then the HSP70 unbinds. If the protein is correctly folded then the HSP70 do not act further, but if incorrectly folded then the protein is acted on in another cycle.

Front 40

HSP60-like protein

Back 40

Also a chaperone. A dimer. Has hydrophobic regions to contain the protein inside the hsp60-like protein. GroES cap added with the use of ATP attachment. Protein folds inside the HSP60-like protein. ATP hydrolyzed, unbinds. Binding of ATP again to decap the GroES and release the protein.

Front 41

Nuclear Pore

Back 41

Entry of proteins into the nucleus. Has Cytosolic fibrils, nuclear basket, membrane ring proteins, scaffold nucleoporins and disordered channel nucleoporins.

Front 42

Ran (nuclear import)

Back 42

RanGDP(inactive) passes through the nuclear pore to be turned into RanGTP by RanGEF, RanGTP is hydrolyzed by Ran-GAP. Ran GTP in the nucleus can bind to either nuclear import or export receptors.

Front 43

Nuclear export receptor

Back 43

Nuclear export receptors bind onto a nuclear export signal on a target protein along with Ran-GTP. binds to the nuclear basket and is exported into cytosol.

Front 44

Nuclear import receptor

Back 44

Nuclear import receptors bind onto nuclear import signals on a target protein in the cytosol and attaches to cytosolic fibril to import into the nucleus. Cargo delivered to nucleus and then the nuclear import receptor binds Ran-GTP in order to exit the nucleus. Ran-GTP is then hydrolyzed in the cytosol in order to return into the nucleus.

Front 45

Secreted and soluble proteins (From ER)

Back 45

Ribosomes can be directed to the ER membrane in order to make polypeptides that are incorporated into the membrane, or into the ER lumen.

Front 46

SRP (Signaling Recognition Particle)

Back 46

SRPs attach themselves to growing polypeptide strands on the Ribosome. They stunt the growth of the peptide until they direct the growing peptide to grow into the ER. SRP, binds to ribosome and growing peptide strand, directs to SRP receptor, transfers ribosome onto protein translocator (pore) on the ER membrane.

Front 47

Soluble proteins (ER Lumen)

Back 47

Hydrophobic sequence binds into translocator, protein synthesis through translocator. Signal peptidase cleaves the transfer sequence.

Front 48

Membrane-bound proteins (ER)

Back 48

+ on cytosolic end, - in ER Lumen. If start transfer and then one stop transfer, or start transfer in the middle, either carboxyl or amine end can be inside or outside depending on charges near the membrane.

Front 49

Multi-pass proteins (ER)

Back 49

Many starts and stops, the first start is cleaved by signal peptidase.

Front 50

Post-translational modification

Back 50

Proteins can be precursors before they enter their final destination. After they enter a certain space, they can be further processed/cleaved into smaller (from larger proteins) proteins that have different functions from one another.

Front 51

Phosphorylation of proteins

Back 51

Phosphorylation of proteins occurs with specific protein kinases. Protein phosphatases remove phosphate groups. There are 3 different kinases that can phosphorylate proteins. Phosphorylation can either activate or deactivate proteins.

Front 52

Serine Kinase

Back 52

Phosphorylates serine groups in target sequences where A-B-Ser-X-X-G

Front 53

Threonine Kinase

Back 53

Phosphorylate threonine in target sequence X-X-Thr-D-E

Front 54

Tyrosine Kinase

Back 54

Phosphorylates tyrosines in target sequence F-X-Tyr-G

Front 55

Localization in the cytosol.

Back 55

Proteins use fat anchors. Myristoyl anchor - amide linkage (n terminus) Palmitoyl uses thiester linkage (cysteine). Farnesyl (prenyl group) uses thioether linkage (CH2-S-CH2).

Front 56

Hedge hog localization

Back 56

Hedgehog is autocleaving in the presence of cholesteral. Cholesterol addition to the signalling domain. Hedge hog then is bound to outside of cell via cholesterol.

Front 57

GPI (glycophosphatidylinositol) anchor

Back 57

Inside (or outside) of ER lumen. Binds to carboxyl terminus of membrane bound protein.

Front 58

Trypanosomes (Trypanosoma Brucei: African Sleeping Sickness)

Back 58

Constant evasion of antibodies/vaccination. Can release coat proteins and generate new proteins in an environment where Immune response is high.

Front 59

GPI in normal cells

Back 59

Tethers protein onto membrane for proximal use.

Front 60

PNH (paroxysmal Nocturnal hemoglobinuria)

Back 60

Defective stem cells turn into mutated red blood cells which don't have coat proteins (GPI-linked) that protect the blood cell from being lysed by our own complement system.

Front 61

Glycosylation

Back 61

N-linked additions occur at sequence of -Asn-X-Ser/Thr-. Will be on N of asparagine. In ER Lumen. Will be added by a oligosaccharyltransferase.

Front 62

Sugar additions

Back 62

Protect proteins, prevents unfolded proteins leaving the ER, and specialized functions for certain proteins.

Front 63

Calnexin

Back 63

Binds glycosylated proteins in order to mediate correct folding. Glucosidase cleaves glucose bound to glycosyl group on glycosylated proteins. If correctly folded, exits from ER. If incorrectly folded glucosyl transferase adds glucose from UDP-Glucose on the glycosyl group. Consistently misfolded proteins can be sent to the proteasome for degradation.

Front 64

Selectins

Back 64

Selectins pull white blood cells towards the endothelial cells. They can slip through between endothelial cells. Selectins bind to glycolipids and glycoproteins that are on the outside of white blood cells. This occurs after tissue damage, endothelial cells will express selectin to recruit white blood cells to the damaged area.

Front 65

Blood typing

Back 65

Different blood types express different kinds of sugars added onto proteins on the surface of blood cells. Type A: GalNac,Fuc. B: Gal, Fuc. AB: Both from A and B. O: Fuc only. O is the universal donor, AB is the universal accepter. Type O has antigens only for O, but AB has antigens for A,B which also happen to fit O. O has the least amount of additions, which will fit into all antigens, but O antigens can only fit O.

Front 66

Regulated Vs. Constitutive release

Back 66

Regulated: Signal required - insulin

Constitutive: no signal required.

Front 67

Histamine Regulated Secretion

Back 67

Histamine is secreted by Mast Cells. Mast Cells store up many vesicles with histamine inside. They release these vesicles upon an allergen signal on a membrane bound antibody (allergic response).

Front 68

ER return pathway

Back 68

KDEL soluble ER resident proteins bind to KDEL receptors in order to return to the ER. Budding from the ER can hold secretory and KDEL resident ER proteins. Secretory proteins will stay in the golgi/ vesicular tubular cluster and KDEL resident ER proteins will rebind KDEL receptors.

Front 69

ExtraCellular Matrix and its components

Back 69

ECM is made up of a variety of different substances with different properties.

There are fibrous proteins for structural (collagen) and adhesive (fibronectin, laminin) purposes.

There are also glyosaminoglycans (GAGs) which are either without (hyaluronan) or with (aggregan) attached proteins.

Front 70

Cartilage

Back 70

Made up of aggregans that are bound to a core protein. Multiple aggrecans make up a cartilage while binding to hyaluronan molecule. They branch off of the hyaluronan using link proteins.

Front 71

Types of Cell signaling

Back 71

Paracrine: Close release of local mediator to many target cells.

Synaptic: Neuron releasing neutransmitters through discharge along the axon into the target cell.

Endocrine: Hormones released from endocrine cell to travel through blood stream and hit target cells

Contact-dependent: cells next to each other with membrane bound signal molecule to another membrane bound receptor.

Front 72

Insulin

Back 72

alpha chain: 21 AA, beta chain: 30 AA.
Promotes glycogen synthesis, stimulates glucose uptake.

Front 73

Thyroid hormone

Back 73

Tyrosine with extra tyrosine ring and also Iodinated. Increases metabolic activity.

Front 74

Thyroid stimulating hormone (TSH)

Back 74

Glycoprotein which causes thyroid to release thyroid hormone. Released by Pituitary gland.

Front 75

Thyroid releasing hormone (TRH)

Back 75

3 AA peptide. Causes pituitary gland to release TSH. Released by hypothalamus.

Front 76

Adrenaline

Back 76

Stimulates glycogenolysis in liver and muscle, increases heart rate.

Front 77

Histamine

Back 77

Causes blood vessels to dilate.

Front 78

Nitric Oxide

Back 78

Causes smooth muscles to relax. Activates GTP ----> cGMP

Front 79

Graves disease

Back 79

Antibodies are bound to TSH receptor causing increased thyroid hormone into the bloodstream. thyroid cell produces and excretes extreme amounts of thyroid hromone will stimulate target cells increasing metabolism.

Front 80

Combinatorial signals

Back 80

Antagonistic or Complementary.

Antagonistic: Both will cause less response, one causes high response.
Complementary: Both will cause response only.

Front 81

Conformational changes by signals

Back 81

Signal molecules can cause a receptor to change conformation.

Front 82

Types of receptors

Back 82

Cytoplasmic: Within the cell, signal crosses membrane.

Extracellular: signal doesn't cross membrane, second messenger sent out by anything signaled on membrane.

Front 83

Types of Receptors (cont.)

Back 83

Ion-Channel coupled receptors

G-Protein coupled Receptors

Enzyme coupled receptors

Front 84

G-Protein Coupled Receptors

Back 84

These are activated by signaling molecules. They recruit and then activate g-proteins according to their catalytic ability.

Front 85

G-Proteins (Ras)

Back 85

Activated by G-Protein Coupled Receptors. Has a GTP added to inactive GDP form (on alpha domain) when bound to G-Protein Coupled receptor with signal. Has three domains (alpha,beta,gamma).

Front 86

Arrestin

Back 86

Arrestin can inactivate GPCR. Activated GPCR can be phosphorylated by GRK( GPCR Kinase) which Arrestin can then bind to. This prevents binding of G-alpha subdomain to GPCR in order to swap GDP to GTP.

Front 87

Receptor recycling

Back 87

Receptors are recycled if endocytosed into a different compartment, they will return to their resident compartment.

Front 88

cAMP Pathway Activation of PKA

Back 88

GPCR signaled by protein G-protein alpha domain activated with GTP. alphadomain will activate adenylyl cyclase which turns ATP to cAMP. cAMP binds to regulatory factors bound to catalytic domain of PKA in order to release free, active PKA which phosphorylates down stream.

Front 89

PKA regulation of gluconeogenesis (with glucagon and adrenaline)

Back 89

Glucagon and adrenaline will activate GPCR which activated G-alpha domain by adding GTP to replace GDP. This activates adenylyl cyclase, increasing cAMP from ATP. Increasing the amount of free active PKA by binding its regulatory subdomains. PKA phosphorylates phosphorylase kinase (activating) which then phosphorylates glycogen phosphorylase (activating) which then phosphorylates glycogen into multiple glucose-1-phosphate, secreting glucose. PKA also phosphorylates glycogen synthase to deactivate it.

Front 90

Activation of transcription by PKA

Back 90

PKA can also phosphorylate certain activators on genes in order to activated the gene to be transcribed.

Front 91

Cholera toxin

Back 91

Contains a KDEL sequence to localize it into the ER. A PDI cleaves the disulfide bond to release an active protein outside of the ER. This active protein adds an ADP-ribose to the G-alpha subdomain in order to keep it in the active state. Cannot hydrolyze GTP. Causes massive dehydration due to cAMP regulated ion pumps. Water flows with the ion out of cells.

Front 92

Ion levels

Back 92

Ion levels within cell maintain homeostasis. Any sort of imbalances will trigger proteins/channels/pumps to activate and either export or import ions.

Front 93

Cystic Fibrosis Transmembrane Conductance Regulater (Cystic Fibrosis)

Back 93

CFTR misfolds due to a 3 AA deletion muitation. Since it's misfolded it's constantly degraded and an inblanace of chlorine in the cell causes abnormal mucus to be made primarily in the lungs. This abnormal mucus can cause inflammation, bacterial build up and infection and damaged lungs.

Front 94

Olfaction

Back 94

GPCR in olfaction (after odorant binding) activates the Galpha domain (GTP) which then activates adenyl cyclase, increasing cAMP and allowing nerve impulse via a flood of Na+.

Front 95

Vision

Back 95

Rhodopsin responds to light in a conformational change, activates G-alpha subunit to activate phosphodiesterase. Converts cGMP to GMP. In presence of GMP, no transmitter is released and bipolar cell becomes active, optic neuron signaled.. In presence of cGMP, Na+ signal, transmitter released to bipolar cell to inhibit it, no optic neuron signal.

Front 96

PI (PIP) Pathway

Back 96

This occurs in MAST CELLS. Pip2 is cleaved by phospholipase c-B. Cleaves it into diacylglycerol still bound onto the membrane and inositol triphosphate (IP3). Phospholipase C-B is activated by a Gprotein signaled by active GPCR (signaled). IP3 signals for calcium released from an IP3 gated calcium channel on the ER membrane. Calcium binds to a protein kinase c (PKC) to activate it when it's bound to the diacylglycerol from PIP2 cleavage to IP3 and DAG.

Front 97

PKC

Back 97

Protein Kinase C has effects of transcriptional regulation through phosphorylation.

Front 98

NO Muscle relaxation

Back 98

Utilizes GPCR signaled by acetylcholine. Causes the IP pathway in endthelial cells. IP3 --> Calcium release causes activated NO synthase. Arginine converted to NO. released into muscle cells, binds to guanylyl cyclase, activates GTP > cGMP. cGMP build up relaxes muscles.

Front 99

Viagra

Back 99

Inhibits phosphodiesterase activity in smooth muscle cells. This inhibits how cGMP turns into GMP thus causing the muscle to further relax due to building up cGMP. Allows the concentration to rise with weak signal.

Front 100

Calcium regulation

Back 100

Calcium is regulated by pumps that either require phosphorylation or swap the Calcium with sodium using the sodium gradient. Calcium is pumped into the ER and mitochondria through pumps also; ATP pump for ER, and a proton gradient pump in mitchondria. Calcium-binding molecules can bind free calcium.

Front 101

Calmodulin

Back 101

Protein that can attach to other proteins in order to modify activity. Calmodulin can bind to phosphorylase kinase. Once calmodulin is bound to calcium it will be active. If calmodulin is bound to both calcium and phosphorylase kinase and phosphorylase kinase is phosphorylated, phosphorylase kinase is hyperactive. Inactive if phosphorylase kinase bound to calmodulin with no calcium and unphosphorylated. Active if only phosphorylated OR calmodulin bound to calcium.

Front 102

Cam Kinase

Back 102

Activated by Calmodulin(with Ca2+) binding to the inhibitory domain. Free catalytic domain phosphorylates targets.

Front 103

Muscle cell movement

Back 103

Adrenaline signals the GPCR, which activates G-Alpha subdomain (GTP bound) which activates the adenyl cyclase to make cAMP from ATP. This activates PKA: inhibiting glycogen synthase, activate the glucogenic pathway (Phosphorylates) phosphorylase kinase which phosphorylates glycogen phosphorylase.

Calcium also rushes into the cell, which hyperactivates phosphorylase kinase( bound to calmodulin), activates CaM kinase(also bound to calmodulin) which inhibits glycogen synthase.

Front 104

Transmembrane Kinases

Back 104

Active kinases which receive a signal protein/molecule from the outside of the cell. Have tyrosine kinase domains. Transphosphorylation activates kinase domains

Front 105

Transphosphorylation

Back 105

occurs on transmembrane kinases.
EGF: One of two monomers interacts with one in which both will become phosphorylated
PDGF: Two monomers interact with each other in which both are phosphorylated.
Insulin: Signals both monomers for transphosphorylated.

Front 106

SH2 domains

Back 106

SH2 domains allow the protein that contains those domains to dock to phosphorylated tyrosines in order for the signal to cascade down to them for activation.

Front 107

Different Transmembrane Kinases

Back 107

Can recruit different combinations of factors by varying their order of phosphorylated tyrosines and proximal amino acid residues.

Front 108

Ras-Monomeric G-Proteins Activation

Back 108

GEF activates it (GTP Bound) GAP inactivates (GDP)
Signal on transphosphorylating membrane proteins will recruit and phosphorylate Grb-2 and also Sos(GEF for Ras)

Front 109

MAPK Pathway

Back 109

MAPKKK will be activated by the Ras-GTP. MAPKKK phosphorylates MapKK which phosphorylates MAPK which phosphorylates specific activators in the nucleus to activate genes, and certain cytosol proteins.

Front 110

Insulin Receptor Pathway

Back 110

Insulin receptors will transphorylate when insulin is bound. This will recruit IRRS and phosphrylate it. Phosphorylated IRS recruits PI3 Kinase, which becomes phosphorylated and also phosphorylates PIP2 to PIP3. PIP3 recruits PDK1 which phosphorylates Akt to activate it. Akt phosphorylates FOXO in order to inhibit gluconeogenic genes. FOXO activates gluconeogenic genes, ends up in the cytosol when phosphorylated.

Front 111

Liver Cell and Akt

Back 111

Active AKT (from PI3 recruiting PDK1, phosphorylating) will inhibit the inhibitor of glycogen synthase, which is glycogen synthase kinase. This double negative causes the presence of active Akt to activate glycogen synthase. Glyc synthase has two phosphorylation sites for glycogen synthase kinase and pka, has additive properties in inhibition.

Front 112

Glucose Transport Stimulation

Back 112

Via insulin. Endosomes contain glucose transport proteins move into the lipid bilayer when insulin is present on the insulin receptor. (Which transphosphorylates)

Front 113

TGF-Beta signaling

Back 113

Signal will bind to a type 1 signal receptor. Type 1 signal receptor bound to signal molecule becomes the signal for a type 2 signal receptor protein on membrane. type 1 phosphorylates type 2 to recruit Smad (and phosphorylate it) Smad-P will activate specific genes (not cytosolic proteins).

Front 114

Hedgehog Signaling

Back 114

Patched inhibits smoothened from binding to the membrane. This leaves Gli to be processed. Processed Gli will inhibit genes which develop forehead and eyes.

If patched binds to hedgehog, this will allow smoothened to bind to the membrane which inhibits gli processing. Unprocessed Gli will activate genes that allow for forehead and eye development

Front 115

Cyclopamine

Back 115

Binds to smoothened when smoothened on the membrane. This inhibits smoothened from inhibiting Gli processing. Gli will be processed and thus genes for forehead and eye development will be inhibited by processed Gli. Patched still endocytosed and degraded.