Open AccessGIT1 Functions as a Scaffold for MEK1–Extracellular Signal-Regulated Kinase 1 and 2 Activation by Angiotensin II and Epidermal Growth Factor
Author(s) -
Guoyong Yin,
Judith Haendeler,
Chen Yan,
Bradford C. Berk
Publication year - 2004
Publication title -
molecular and cellular biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.14
H-Index - 327
eISSN - 1067-8824
pISSN - 0270-7306
DOI - 10.1128/mcb.24.2.875-885.2004
Subject(s) - proto oncogene tyrosine protein kinase src , biology , microbiology and biotechnology , g protein coupled receptor , grb2 , epidermal growth factor , signal transduction , scaffold protein , sh3 domain , map kinase kinase kinase , kinase , angiotensin ii , tyrosine kinase , mapk/erk pathway , mitogen activated protein kinase kinase , protein kinase a , receptor , biochemistry
Activation of the mitogen-activated protein kinase pathway represented by extracellular signal-regulated kinases (ERK1/2) and activation of the upstream kinase (MEK1) are critical events for growth factor signal transduction. c-Src has been proposed as a common mediator for these signals in response to both G protein-coupled receptors (GPCRs) and tyrosine kinase-coupled receptors (TKRs). Here we show that the GPCR kinase-interacting protein 1 (GIT1) is a substrate for c-Src that associates with MEK1 in vascular smooth-muscle cells and human embryonic kidney 293 cells. GIT1 binding via coiled-coil domains and a Spa2 homology domain is required for sustained activation of MEK1-ERK1/2 after stimulation with angiotensin II and epidermal growth factor. We propose that GIT1 serves as a scaffold protein to facilitate c-Src-dependent activation of MEK1-ERK1/2 in response to both GPCRs and TKRs.