cst-2-gpcr and downstream signal-new_图文.pptVIP

cAMP-dependent Activation of PKA In most animal cells, cAMP exerts its effects mainly by activating cAMP-dependent protein kinase (PKA). PKA phosphorylates specific serines or threonines on selected target proteins PKA consists of two catalytic subunits and two regulatory subunits. cAMP binds to the regulatory subunits and alters their conformation, causing them to dissociate from the complex. The released catalytic subunits are thereby activated. Regulation of gene expression by cAMP-PKA Some responses mediated by cAMP depend on changes in the transcription of specific genes and take hours to develop fully. The cAMP response element (CRE) is found in the regulatory region of many genes activated by cAMP. A specific gene regulatory protein called CRE-binding protein (CREB) recognizes CRE sequence. When PKA is activated by cAMP, it phos-phorylates CREB on a single serine; phosphorylated CREB then recruits a transcriptional coactivator called CREB-binding protein (CBP), which stimulates the transcription of the target genes. PKA Mediates Most of the Effects of cAMP Over one hundred PKA substrates have been described. Most of these carry out different functions. How PKA phosphorylates the appropriate substrates in response to a particular stimulus, in a particular cell type? 2.5.2 GPCR Mediated Activation of Phospholipase C Many GPCRs exert their effects mainly via G proteins called Gq that activate the plasma membrane-bound enzyme phospholipase C-b (PLCb). The activated PLCb then cleaves the PIP2 to generate two products: inositol 1,4,5-trisphosphate (IP3) diacylglycerol (DAG). IP3 and Ca2+ Inositol 1,4,5-Trisphosphate (IP3) Triggers Release of Ca2+ from the Endoplasmic Reticulum Ca2+ Functions as a Ubiquitous Intracellular Mediator The most important Ca2+-binding proteins is calmodulin (钙调蛋白) which help to relay the cytosolic Ca2+ signal, Calmodulin functions as a multipurpose intracellular Ca2+ receptor, governing many Ca2+-regulated processes. It