G-PROTEIN-LINKED RECEPTORS AS TYROSINE KINASE SUBSTRATES - NEW PARADIGMS IN SIGNAL INTEGRATION

Understanding how cells integrate signals from a variety of chemically diverse information containing molecules into complex, orchestrated r esponses such as cell proliferation, differentiation and apoptosis is an overarching goal of cell biology. The ligand molecules that act upo n cell surface receptors include those mediating proximal aspects of s ignal transduction through two major pathways: those that are G protei n linked and those that are tyrosine kinase linked. G-protein receptor s in the hundreds operate by means of less populous groups of heterotr imeric G proteins and the effectors regulated by G proteins. Growth fa ctor receptors with intrinsic tyrosine kinase activity constitute a re latively large group of receptors, which share several downstream sign alling elements with the G-protein-linked receptors. Integration betwe en these two dominant pathways has been observed at several levels. Th e most proximal and intimate interaction possible-that between G-prote in-linked receptors and tyrosine kinase receptors - has been discovere d. Emerging data reveal new paradigms in which phosphorylation oi G-pr otein-linked receptors on specific tyrosyl residues by tyrosine kinase s enable G-protein-linked receptors to interact with adaptor molecules and enzymes previously thought to be restricted only to the signallin g derivative oi tyrosine kinase receptors. CELL SIGNAL 10;8:523-527, 1 998. (C) 1998 Elsevier Science Inc.