Activation of tyrosine kinase of EGFR induces Gbetagamma-dependent GRK-EGFR complex formation.
This study demonstrated that activation of tyrosine kinase of epidermal growth factor receptor (EGFR) induces its association with G protein-coupled receptor kinase 2 (GRK2). Immunoprecipitation experiments showed that EGF stimulation increased GRK2 binding to EGFR complex in HEK293 cells coexpressing EGFR and GRK2. The EGF-induced GRK2-EGFR complex formation was greatly reduced by perturbation of EGFR and Src tyrosine kinase activity. Furthermore, studies with GRK2 mutants showed that neither catalytic activity nor the N-terminal domain of GRK2 was required for EGF-induced GRK2-EGFR complex formation. However, overexpression of Gbetagamma scavengers blocked EGF-induced formation of GRK2-EGFR complex.
Gao
Jingxia
J
Pharmacology Research Center, Shanghai Medical College, Fudan University, 138 Yi Xue Yuan Road, Shanghai 200032, China.
Li
Jiali
J
Chen
Yuejun
Y
Ma
Lan
L
D002460:Cell Line; D017868:Cyclic AMP-Dependent Protein Kinases / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D004789:Enzyme Activation; D004815:Epidermal Growth Factor / Q000494:pharmacology / Q000502:physiology; D066246:ErbB Receptors / Q000032:analysis / Q000187:drug effects / Q000378:metabolism*; D044387:GTP-Binding Protein beta Subunits / Q000378:metabolism*; D044388:GTP-Binding Protein gamma Subunits / Q000378:metabolism*; D006801:Humans; D047468:Immunoprecipitation; D009154:Mutation / Q000235:genetics; D051552:beta-Adrenergic Receptor Kinases; D019061:src-Family Kinases / Q000378:metabolism
D044387:GTP-Binding Protein beta Subunits; D044388:GTP-Binding Protein gamma Subunits; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D019061:src-Family Kinases; D017868:Cyclic AMP-Dependent Protein Kinases; D051552:beta-Adrenergic Receptor Kinases