Related Experiment Video
Updated: Aug 29, 2026
A Functional Assay for Gap Junctional Examination; Electroporation of Adherent Cells on Indium-Tin Oxide
Published on: October 18, 2014
GIT1 functions as a scaffold for MEK1-extracellular signal-regulated kinase 1 and 2 activation by angiotensin II and
Guoyong Yin1, Judith Haendeler, Chen Yan
1Center for Cardiovascular Research and Department of Medicine, University of Rochester, 601 Elmwood Avenue, Rochester, NY 14642, USA.
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.
Insights
GPCR kinase-interacting protein 1 (GIT1) acts as a scaffold protein, linking c-Src to MEK1. This interaction is crucial for sustained activation of the MEK1-ERK1/2 pathway in response to growth factors.
Area of Science:
- Cellular signaling pathways
- Molecular biology
- Signal transduction
Background:
- Mitogen-activated protein kinase (MAPK) pathway activation, involving extracellular signal-regulated kinases (ERK1/2) and MEK1, is vital for growth factor signaling.
- c-Src kinase is implicated as a common mediator for signals from G protein-coupled receptors (GPCRs) and tyrosine kinase-coupled receptors (TKRs).
Purpose of the Study:
- To investigate the role of GPCR kinase-interacting protein 1 (GIT1) in mediating signal transduction pathways.
- To determine if GIT1 functions as a scaffold protein in the c-Src-dependent activation of the MEK1-ERK1/2 pathway.
Main Methods:
- Investigated GIT1 as a substrate for c-Src.
- Examined GIT1 association with MEK1 in vascular smooth-muscle cells and human embryonic kidney 293 cells.
- Assessed the requirement of GIT1 domains for MEK1-ERK1/2 activation upon stimulation with angiotensin II and epidermal growth factor.
Main Results:
- GIT1 is a substrate for c-Src and associates with MEK1.
- GIT1 binding, mediated by coiled-coil and Spa2 homology domains, is essential for sustained MEK1-ERK1/2 activation.
- This sustained activation occurs following stimulation by both angiotensin II (GPCR agonist) and epidermal growth factor (TKR agonist).
Conclusions:
- GIT1 acts as a scaffold protein in the vascular smooth-muscle cells and HEK 293 cells studied.
- GIT1 facilitates c-Src-dependent activation of the MEK1-ERK1/2 pathway.
- The findings suggest GIT1 is a key mediator for both GPCR and TKR signaling pathways.
Related Concept Videos
01:07MAPK Signaling Cascades
01:22Amplifying Signals via Enzymatic Cascade
01:17Intracellular Signaling Affects Focal Adhesions
Some...
01:24Small GTPases - Ras and Rho
Three regulatory proteins control their activity:
02:38Mitogens and the Cell Cycle
01:19Interactions Between Signaling Pathways
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...