Regulation of tyrosine kinase cascades by G-protein-coupled receptors.
Mitogenic signaling by G-protein-coupled receptors (GPCRs) involves tyrosine phosphorylation of adaptor proteins and assembly of multiprotein Ras activation complexes. Over the past three years, three types of scaffolds for GPCR-directed complex assembly have been identified: transactivated receptor tyrosine kinases (RTKs), integrin-based focal adhesions, and GPCRs themselves. Nonreceptor tyrosine kinases play an important role in each case. The processes of GPCR desensitization and sequestration via clathrin-coated pits are also involved in signaling through the RTK- and GPCR-based scaffolds.
Luttrell
L M
LM
The Howard Hughes Medical Institute, Departments of Medicine, Surgery and Biochemistry, Box 3821, Duke University Medical Center, Durham, NC 27710, USA.
Daaka
Y
Y
Lefkowitz
R J
RJ
D000818:Animals; D019390:Arrestins / Q000502:physiology; D002448:Cell Adhesion; D002966:Clathrin / Q000502:physiology; D004705:Endocytosis; D004789:Enzyme Activation; D019204:GTP-Binding Proteins / Q000502:physiology*; D008954:Models, Biological; D011499:Protein Processing, Post-Translational; D011505:Protein-Tyrosine Kinases / Q000502:physiology*; D011956:Receptors, Cell Surface / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D000071557:beta-Arrestins; D019061:src-Family Kinases / Q000502:physiology
D019390:Arrestins; D002966:Clathrin; D011956:Receptors, Cell Surface; D000071557:beta-Arrestins; D011505:Protein-Tyrosine Kinases; D019061:src-Family Kinases; D019204:GTP-Binding Proteins