Activation of the ERK/ MAPK pathway by an isoform of rap1GAP associated with G alpha(i).
Many receptors for neuropeptides and hormones are coupled with the heterotrimeric G(i) protein, which activates the p42/44 mitogen-activated protein kinase ( ERK/ MAPK) cascade through both the alpha- and betagamma-subunits of G(i). The betagamma-subunit activates the ERK/ MAPK cascade through tyrosine kinase. Constitutively active G(alpha)i2 (gip2) isolated from adrenal and ovarian tumours transforms Rat-1 fibroblasts and also activates the ERK/ MAPK cascade by an unknown mechanism. The ERK/ MAPK pathway is activated by Ras, and is inhibited when the low-molecular-mass GTP-binding protein Rap1 antagonizes Ras function. Here we show that a novel isoform of Rapl GTPase-activating protein, called rap1GAPII, binds specifically to the alpha-subunits of the G(i) family of heterotrimeric G-proteins. Stimulation of the G(i)-coupled m2-muscarinic receptor translocates rap1GAPII from the cytosol to the membrane and decreases the amount of GTP- bound Rap1. This decrease in GTP-bound Rap1 activates ERK/ MAPK. Thus, the alpha-subunit of G(i) activates the Ras-ERK/ MAPK mitogenic pathway by membrane recruitment of rap1GAPII and reduction of GTP- bound Rap1.[1]References
- Activation of the ERK/MAPK pathway by an isoform of rap1GAP associated with G alpha(i). Mochizuki, N., Ohba, Y., Kiyokawa, E., Kurata, T., Murakami, T., Ozaki, T., Kitabatake, A., Nagashima, K., Matsuda, M. Nature (1999) [Pubmed]
Annotations and hyperlinks in this abstract are from individual authors of WikiGenes or automatically generated by the WikiGenes Data Mining Engine. The abstract is from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.About WikiGenesOpen Access LicencePrivacy PolicyTerms of Useapsburg
