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Transcript
Cell Communication Chapter 15Part I- General signaling strategies Part II- G protein signaling Part III- Enzyme-linked cell surface receptors Part IV- Proteolysis-dependent signaling pathways Outline Part I- General signaling strategies A. Two cell types B. A typical signaling pathway C. Most signaling molecules are hydrophilic (water loving) D. Some signaling molecules are hydrophobic (water hating) E. A review of membranes (from chapter 10) F. Signaling over short or long distances G. Autocrine signaling H. Cells respond to specific combinations of factors I. Signaling through gap junctions J. Different cells respond differently to the same signal molecules K. Nuclear receptors are ligand-activated gene regulatory proteins L. Three classes of cell-surface receptors M. Common features of G protein-linked and enzymelinked receptors Part II- G protein signaling A. G protein-linked receptors B. Trimeric GTP-binding proteins (G proteins) relay the signal C. Steps to activate a G protein PATHWAY 1 - cAMP D. cAMP-mediated transduction E. Examples of hormone-induced cell responses mediated by cAMP F. Some examples of phospholipase C-b cell responses- PATHWAY 2- Phospholipase C-b G. Overview of phospholipase C-b pathway H. We can activate these pathways with drugs I. Ca++ is a ubiquitous intracellular messenger J. G-protein linked receptors required for vision and smell K. How is a response desensitized? L. Summary Part II- G protein signaling A. G protein-linked receptors •______ membrane proteins •__% of C. nematode genes •~_____ G proteins used for _____ in mice •Activated by ___________ __________,____________ B. Trimeric GTP-binding proteins (_______) relay the signal Three subunits- _________ INACTIVE G protein 1. Inactive state- a subunit bound with ______ 2. a, b and g subunits in one complex Part II- G protein signaling C. Steps to activate a G protein 1. Signal molecule binds ____________ 2. G protein _________ with receptor 3. GDP is replaced by _____ on __ subunit 4. ____ proteins dissociate from __ subunit Part II- G protein signaling 5. a subunit binds to and ______ a ____________ 6. GTP on a subunit is _________ to _____ 7. a subunit __________ with b/g subunits Part II- G protein signaling PATHWAY 1 - cAMP D. cAMP-mediated transduction 1. Signal molecule binds _________ 2. G protein interacts with receptor, ____ is replaced by ____, and _________ dissociate from a subunit G protein is termed “__” in this pathway 3. A subunit interacts with ___________________ 4. ____ is converted to ______ PATHWAY 1 - cAMP What does cAMP look like?? 1. ___________ produces ____ This is the “Target” protein for the G- protein designated ___ 2. Note that ________ binds both __ and __ carbons of dATP ribose, hence the name “________” 3. cAMP ___________ breaks cAMP down to _______ Part II- G protein signaling PATHWAY 1 - cAMP Part II- G protein signaling 5. cAMP binds ____________________ (PKA) •PKA action likely accounts for all ___________ effects •PKA is composed of _______________ subunits and _____ __________ subunits 6. Binding of cAMP causes active subunits to __________ and become “___________” PATHWAY 1 - cAMP Part II- G protein signaling 7. Activated PKA is transported into ______________. 8. PKA_____________ CRE-binding protein (______). 9. CREB interacts with cofactor ____, which activates gene ____________. Part II- G protein signaling PATHWAY 1 - cAMP E. Examples of hormone-induced cell responses mediated by cAMP Target tissue Hormone Major response Muscle ___________ ____________________ Heart Fat Ovary __________ ____________________ _____________ _________________ _________ __________ ____________________ cAMP induction by serotonin Red = High level cAMP Yellow = Moderate level cAMP Blue = Low level cAMP Part II- G protein signaling PATHWAY 2- Phospholipase C-b F. Some examples of phospholipase C-b cell responses- Smooth muscle contraction, blood platelet aggregation, glycogen breakdown 1. Signal molecule binds receptor 2. G protein interacts with receptor, GDP is replaced by GTP, and b/g proteins dissociate from a subunit G protein is termed “__” in this pathway 3. __activates phospholipase C-b a. ____ Activates protein ________ Release of Ca++ from ___________ ____________ PI4,5-bisphosphate b. ___ 4. phospholipase C-b breaks down _____ ____________ into: a. ______ b. _____ PATHWAY 2- Phospholipase C-b Part II- G protein signaling G. Overview of phospholipase C-b pathway ____activates protein kinase C (PKC) ___ binds a IP3gated __________ channel Part II- G protein signaling PATHWAY 2- Phospholipase C-b H. We can activate these pathways with drugs Drug Effect a. DAG ______________ ____________ b. IP3 __________________ __________________ _____________________ Ca++ release via a non-G protein pathway: __________ interaction I. Ca++ is a ubiquitous intracellular messenger Part II- G protein signaling a. Free Ca++ in cytoplasm is <____ M, b. Extracellular is _____ M c. Ca++-_______ pumps Ca++ out of cell and into ___ Example- Nerve cells_____________, influx of Ca++, secretion of ____________________ How is the Ca++ signal transduced?? Through ______________ 1. Ca++ binds ___________ 2. This complex binds ______________ 3. CaM kinases ______________ other proteins Part II- G protein signaling One CaM kinase is important in ____________ If knock out _____________ in miceDefect in ____________ where things are in _____ Part II- G protein signaling J. G-protein linked receptors required for ______ and _______ Humans- distinguish >__________ distinct smells How?- by 1000s of __________ olfactory receptors (____) 1. 2. 3. 4. 5. 6. ________ binds receptor _____________ activated ________ produced Gate opened ____ infux Initiate __________ to brain ____________ also use G-proteins Termed “____“ operates through ______ production K. How is a response _______________? Part II- G protein signaling ____, _____ or other G-linked receptor kinases (______) ______________the receptor ________ then binds the phosphorylated receptor • GTP converted to ____ on a subunit • IP3 __________________ • Ca++ pumped ______ • cAMP _____________ Mechanisms of inactivating responses Part II- G protein signaling L. Summary G-protein linked receptors act through G proteins G protein Gs Gq Golf Gt Target Enzyme _____________ _______________ Molecule made Target _____ _____ ____ __________, __________ ______ _______ _______________ _______ __________ __________ ____________ _____ ___________ _________ PKC, PKA and CaM kinases all phosphorylate target proteins on________ or __________residues