"GIT"ing MAP Kinase Activated

Science's STKE  13 Jan 2004:
Vol. 2004, Issue 215, pp. tw20-TW20
DOI: 10.1126/stke.2152004TW20

The GIT (G protein-coupled receptor kinase-interacting protein) family of proteins appear to function in modulating signaling through both G protein-coupled receptors (GPCRs) and receptor tyrosine kinases. GIT proteins are implicated in regulation of receptor internalization, control of vesicle trafficking, and regulation of focal adhesions and cytoskeletal organization. The GIT proteins have guanosine triphosphatase-activating activity but also bind other regulatory proteins. A yeast two-hybrid search for new binding partners of GIT1 turned up the mitogen-activated protein kinase kinase MEK-1. The endogenous proteins in rat vascular smooth muscle cells were shown to associate in immunoprecipitates. Decreasing the abundance of GIT1 with RNA interference or antisense oligonucleotides inhibited activation of the mitogen-activated protein kinases ERK1 and ERK2 by both angiotensin II, which activates a GPCR, and epidermal growth factor, which activates a receptor tyrosine kinase. The authors suggest that GIT1 could help localize and promote ERK activation at particular sites such as focal adhesions.

G. Yin, J. Haendeler, C. Yan, B. C. Berk, GIT1 functions as a scaffold for MEK1-extracellular signal-regulated kinase 1 and 2 activation by angiotensin II and epidermal growth factor. Mol. Cell. Biol. 24, 875-885 (2004). [Abstract] [Full Text]