Interaction of a Receptor Tyrosine Kinase, EGF-R, with Caveolins: CAVEOLIN BINDING NEGATIVELY REGULATES TYROSINE AND SERINE/THREONINE KINASE ACTIVITIES *

摘要: Caveolin, a 21–24-kDa integral membrane protein, is principal component of caveolae membranes. We and others have suggested that caveolin functions as scaffolding protein to organize concentrate certain caveolin-interacting signaling molecules within In this regard, it has been shown 20-amino acid membrane-proximal region the cytosolic NH2-terminal domain sufficient mediate interaction with proteins, namely G-proteins, Src-like kinases, eNOS, H-Ras. This caveolin-derived termed caveolin-scaffolding domain. Binding functionally suppresses activity G-protein α subunits, suggesting binding may also play negative regulatory role in signal transduction. Here, we report direct growth factor receptor, EGF-R, known caveolae-associated receptor tyrosine kinase. Two consensus motifs previously defined using phage display technology. One these present conserved kinase domains most kinases (termed IX). now show motif EGF-R can caveolins 1 3 but not 2. addition, both inhibit autophosphorylation kinasein vitro. Importantly, caveolin-mediated inhibition could be prevented by addition an EGF-R-derived peptide (i) contains well (ii) located kinases. Similar results were obtained C, serine/threonine kinase, function general inhibitor. The implications our are discussed context caveolae-mediated caveolae-coupled might explain how linear pathways branch interconnect extensively, forming module or network.