Regulation of Signal Transduction by G Proteins in Exocrine Pancreas Cells
The second messenger for hormone-induced Ca2+ release is inositol 1,4,5-triphosph ate (IP3) . Following binding of an agonist to its receptor, phospholipase C (PLC) is activated and phosphatidylinositoI4,5-bisphosphate is broken down to IP3 and diacylglycerol (Fig. 1). While IP3 releases Ca2+ from a nonmitochondrial compartment, which is most likely the endoplasmatic reticulum , diacylglycerol activates protein kinase C which in many cells leads to the final cell response by kinase C mediated phosphorylation of target proteins . IP3 can be metabolized by dephosphorylation to inositol 1,4-bisphosphate (IP2) or by phosphorylation to inositol 1,3,4,5-tetrakisphosphate (IP4), which is supposed to be involved in Ca2+ influx into the cell, the mechanism of which is yet not quite clear. The two molecules IP4 and IP3 seem to act together to control Ca2+ influx [5, 8]. A current model is based on the hypothesis that Ca2+ enters the cell through an IP3-sensitive Ca2+ pool in a manner similar to that proposed by Putney [10, 11], and that IP3 modulates Ca2+ entry into that Ca2+ store . Thus, the Ca2+ pool can be filled from the outside of the cell, and Ca2+ influx takes place only if the pool is emptied due to IPrinduced Ca2+ release. IP4 is dephosphorylated to inositol 1,3,4-trisphosphate of which a second messenger function is not yet known. Evidence suggests that in receptor-mediated activation of PLC GTP-binding proteins (G proteins) are involved .
KeywordsAcinar Cell Cholera Toxin Vasoactive Intestinal Polypeptide Pertussis Toxin Pancreatic Acinar Cell
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