Regulation of Signal Transduction by G Proteins in Exocrine Pancreas Cells

Abstract

The second messenger for hormone-induced Ca²⁺ release is inositol 1,4,5-triphosph ate (IP₃) [14]. 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 [15], diacylglycerol activates protein kinase C which in many cells leads to the final cell response by kinase C mediated phosphorylation of target proteins [9]. 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 [8]. 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 [3].