The protein-tyrosine phosphatase TCPTP regulates epidermal growth factor receptor-mediated and phosphatidylinositol 3-kinase-dependent signaling.

摘要: In this study we have investigated the down-regulation of epidermal growth factor (EGF) receptor signaling by protein-tyrosine phosphatases (PTPs) in COS1 cells. The 45-kDa variant PTP TCPTP (TC45) exits nucleus upon EGF activation and recognizes as a cellular substrate. We report that TC45 inhibits EGF-dependent c-Jun N-terminal kinase, but does not alter extracellular signal-regulated kinase 2. These data demonstrate can regulate selectively mitogen-activated protein pathways emanating from receptor. receptor-mediated signaling, PKB/Akt 2, function downstream phosphatidylinositol 3-kinase (PI 3-kinase). found TC45-D182A mutant, which is capable forming stable complexes with substrates, inhibit almost completely PI PKB/Akt. act upstream 3-kinase, most likely inhibiting recruitment p85 regulatory subunit Recent studies indicated be activated absence following integrin ligation. find integrin-mediated cells abrogated specific inhibitor tyrphostin AG1478, attachment to fibronectin. Thus, may serve negative regulator or integrin-induced, signaling.