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PMID: 14701758 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

GIT1 functions as a scaffold for MEK1-extracellular signal-regulated kinase 1 and 2 activation by angiotensin II and epidermal growth factor.

Molecular and cellular biology ·Vol. 24 ·No. 2 ·2004-01-00 ·Pages 875-85

Yin G, Haendeler J, Yan C, Berk BC

Abstract

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.

MeSH Terms
Adaptor Proteins, Signal Transducing Angiotensin II/pharmacology Animals Base Sequence Binding Sites Cell Cycle Proteins Cell Line Cells, Cultured DNA, Complementary/genetics Enzyme Activation/drug effects Epidermal Growth Factor/pharmacology GTPase-Activating Proteins/chemistry,genetics,metabolism HeLa Cells Humans In Vitro Techniques MAP Kinase Kinase 1 MAP Kinase Signaling System Mice Mitogen-Activated Protein Kinase 1/metabolism Mitogen-Activated Protein Kinase 3 Mitogen-Activated Protein Kinase Kinases/metabolism Mitogen-Activated Protein Kinases/metabolism Models, Biological Muscle, Smooth, Vascular/drug effects,metabolism Mutagenesis Phosphoproteins Phosphorylation Protein Structure, Tertiary RNA Interference Rats Receptor Protein-Tyrosine Kinases/metabolism Receptors, G-Protein-Coupled/metabolism Two-Hybrid System Techniques
Chemicals
Adaptor Proteins, Signal Transducing Cell Cycle Proteins DNA, Complementary GIT1 protein, human GTPase-Activating Proteins Git1 protein, mouse Git1 protein, rat Phosphoproteins Receptors, G-Protein-Coupled Angiotensin II Epidermal Growth Factor Receptor Protein-Tyrosine Kinases Mitogen-Activated Protein Kinase 1 Mitogen-Activated Protein Kinase 3 Mitogen-Activated Protein Kinases MAP Kinase Kinase 1 MAP2K1 protein, human Map2k1 protein, mouse Mitogen-Activated Protein Kinase Kinases
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Yin Guoyong
Center for Cardiovascular Research and Department of Medicine, University of Rochester, 601 Elmwood Avenue, Rochester, NY 14642, USA.
Haendeler Judith
Yan Chen
Berk Bradford C
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.24.2.875-885.2004
Published
2004-01-00
Pages
875-85
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC343801
Subset
IM
Grants
NHLBI NIH HHS · R01 HL049192 · United States
NHLBI NIH HHS · R01 HL063462 · United States
NHLBI NIH HHS · R01 HL 49192 · United States
NHLBI NIH HHS · R01 HL 59975 · United States
External Links
PubMed source DOI: 10.1128/MCB.24.2.875-885.2004 PMC Full Text View journal details
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