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49 Cards in this Set
- Front
- Back
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what type of signaling occurs at a distance? and eg
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endocrine
hormone secretion by endocrine gland |
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what type of signaling occurs at a close range?
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paracrine
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what type of signaling occurs to the same cell?
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autocrine
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what type of signaling occurs when receptor and ligand are attached to cell surfaces? and eg
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cell surface to cell surface
eg integrin |
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what type of receptor is embedded in plasma membrane?
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transmembrane receptors are integral membrane proteins
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what type of receptor is located within the cytoplasm? what is their function?
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intracellular receptor, bind to ligands adn either diffuse or are transported in to cytoplasm
-function as transcription factors that directly regulate transcription on target genes |
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egs of things G-protein coupled receptors are for
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-light, odor molecules
-histamine, dopamine, serotonin -protein and peptide hormones |
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structure of G-protein coupled receptors
-what is the ligand binding domain? -how many transmembrane domains? -what are the subunits? |
-N-terminus contains ligand binding domain
-7 transmembrane domains -3 subunits- alpha, beta, gamma |
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function of adenyl cyclase?
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converts ATP to cAMP
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what is the negative regulator of cAMP?
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-cAMP levels controlled by cAMP phosphodiesterases which cleave cyclic nucleotide on AMP
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what does cAMP activate? and what is its function?
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protein kinase A (PKA)- serine threonine protein kinase that phosphorylates metabolic enzymes
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what is the structure of PKA?
how many molecules of its activator are required? how does it function? |
4 subunits- 2 catalytic, 2 regulatory
-1 cAMP binds to each subunit -catalytic dissociate and phosphorylate and regulate PKA target proteins |
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what G-protein subunit stimulates adenyl cyclase? inhibits?
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G alpha s
G alpha i |
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what G-protein subunit stimulates phospholipase C beta
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G alpha q
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what phosphorylates PIP2? what are the products?
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phospholipase C (PLCbeta)
-produces IP3 and DAG |
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what is the role of IP3? DAG?
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-IP3 binds to Ca channels on ER causing Ca release, necessary for activation of PKC
-DAG binds directly to PKC to activate; on membrane |
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what is the structure of PKC?
where/what is its function? |
monomer with regulatory and catalytic domains
-regulatory domains bind Ca and DAG -activated PKC is bound to membrane |
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list eg of Ca regulated proteins
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Cl channels (secretion)
K+ channels (membrane potentials) PKC adenyl cyclase nitrix oxide synthetase |
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what is the function of calmodulin? what is its binding potential?
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-Ca chaperone, protein that shuttles Ca where it needs to go
-can bind 4 Ca molecules |
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describe NO
-how does it enter cells? -what does it activate? |
-oxygen containing free radical, in small concentrations essential for cellular function
-activates guanylate cyclase which produces cGMP from GTP |
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what is NO required for? (3)
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-smooth muscle relaxation
-vasodilation, inc blood flow -angiogenesis (growth of new blood cells) |
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structure and function of epidermal growth factor (EGF) receptor (also called Erb-B)
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-ligand binds and causes dimerization
-dimerization generates active site that catalyzes cross-phosphorylation on tyr residues of each dimer -effector proteins have SH2 domains that bind to p-tyr |
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what family of tyr kinase receptors can form heterodimers? what is the significance?
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EFG receptors (ErbB FAMILY)
-increases specificity and complexity of signaling cascades |
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what is the structure of the insulin receptor?
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heterotetramer
-2 alpha (linked via disulfide linkage) that bind insulin -2 beta transmembrane that upon insulin binding, domains open and tyr kinase domains on beta catalyze cross phosphorylation on multiple tyr residues |
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what is the significance of IRS
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insulin receptor substrate, phosphorylated by receptor on multiple tyr residues
-phosphorylation allows for docking and activation of effector molecules |
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eg of effector molecules activated by phosphorylation by IRS1
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rb2
PLCgamma (promotes IP3 AND DAG formation) PI3 Kinase |
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function of PI-3 kinase
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converts lipid PIP2 to PIP3
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what is the function of PIP3
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membrane docking site for proteins with pleckstrin homology (PH) domains
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eg of proteins that bind to PH domains?
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PKB/Akt- serine threonine kinase
PDK1 |
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function of PKB/Akt
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regulates GLUT4 translocation and signaling pathways involved in cell growth (transcription factors), proliferation, cell survival and protein synthesis
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what is the major cell survival factor involved with activation of PKB?
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phosphorylation of BAD (pro-apoptotic protein)
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what is the sensor of nutrient levels? via activation of PKB
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mTOR activation by PKB; imp for control of autophagy and controller of protein synthesis
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what is function/significance of JAK?
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JAK-STAT receptors do not have intrinsic tyr kinase activity
-bind JAK after ligand binds and receptor dimerizes -JAK cross phosphorylate each other and receptor |
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what is function/significance of STAT?
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-STAT binds to p-tyr site via SH2 domain
-JAK phosphorylates STAT which dimerizes and dissociates -translocate to nucleus to activate transcription of target genes |
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structure/function of receptor serine-threonine kinases?
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-most prominent receptors
-obligate heterodimers -generally composed of type 1 and 2 receptors, each with serene-threonine kinase domain |
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eg of ligand that binds to serine-threonine kinase receptor
-which receptor does it bind to? |
-TGF-beta binds to type 2 receptor
-type 2 receptor recruits and phosphorylate type 1 |
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what is meant by obligate heterodimer?
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-receptor serine-threonine kinase is a obligate heterodimer
-type 2 receptor does not signal to SMADs, only type 1 does- obligate heterodimer |
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what/where is phosphorylated on serine threonine kinase receptor?
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R-Smads are phosphorylated on series by activated type 1 receptor
-phosphorylated R-smads dissociate and form complex with Co-Smad (Smad 4) which translocates to nucleus -binds cis acting elements regulating transcription |
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what is TGF-beta? what is its function?
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transforming growth factor
-multifunctional cytokine -function: differentiation and development stimulation of extracellular matrix synthesis and deposition inflammation and allergy generally anti-proliferative and inhibits cell growth epithelial to mesenchymal transitions and metazoic cancer |
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3 families of ion channel receptors
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-cys loop pentamer
-glutamate receptor-tetramer -P2X family-trimer |
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nicotinic acetylcholine receptor function
what enters/exits? |
Na/K channel consisting of 5 subunits
Na in, K out |
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what receptor opens a Cl channel?
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GABAa
-Cl in and reduction in neurotransmission by inhibiting action potentials |
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eg of Cys-loops family receptors
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serotonin 5-HT3
ligand gated contains 4 transmembrane domains controls flux of Ca |
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what type of receptor can regulate gene expression?
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nuclear hormone receptors are transcription factors
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what are the domains in nuclear hormone receptors?
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ligand (hormone) binding domain
DNA binding domain transcriptional activation domain |
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true/false- steroid hormones can diffuse across the lipid membrane?
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true, then bind to nuclear receptor which when activated act as transcription factors that directly regulate gene expression
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eg of dysregulated pathways during cancer development
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-Ras>MAPK-->Cell proliferation
eg 95% pancreatic cancers have constitutive activation of Ras |
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how does PI3 Kinase activation lead to cell survival?
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phosphorylates and inhibits BAD
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activation of what can inc cell proliferation and secretion of angiogenic factors? how?
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activated EGF
-affects surround vasculature can lead to inc blood vessel supply and inc growth and tumor metastasis |
