ras proto-oncogene protein (p21ras)
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Function
- membrane-bound guanine nucleotide-binding proteins;
- cycles between active guanosine-triphosphate (GTP) bound form & inactive guanosine-diphosphate (GDP) bound form;
- has weak intrinsic GTPase activity
- p21ras binds to & activates raf1 protein probably in association with other proteins; raf1 activates MEK which in turn activates MAP kinases
- p21ras acts downstream of receptor tyrosine kinases, (EGFR, insulin) & src via GRB2 & SOS
- regulators of p21 ras include:
- GTPase-activating proteins
- guanine nucleotide exchange factors
Pathology
- the oncogenic protein V12ras in which Gly-12 is mutated to Val results in a protein locked in its GTP-bound form[5].
Genetics
- 4 subtypes are 'true' ras proteins[4]
- p21ras subtypes encoded by separate genes; sequence variability resides in carboxy terminus
Notes
p21ras is required for differentiation of PC-12 cells, but not NGF-mediated survival. It appears the actions of NGF on survival of PC-12 cells is mediated through PI-3-kinase, independent of p21ras.
More general terms
More specific terms
- H-ras proto-oncogene protein (Harvey ras, p21Hras, Ha-ras)
- K-ras proto-oncogene protein (Kirsten ras)
- N-ras proto-oncogene protein (neuroblastoma ras, NRAS)
Additional terms
- FXYD domain-containing ion transport regulator 3 (Cl- conductance inducer protein Mat-8, mammary tumor 8 kD protein, phospholemman-like, FXYD3, MAT8, PLML)
- ras signal transduction
References
- ↑ Kahn RA, Der CJ, Bokoch GM. The ras superfamily of GTP-binding proteins: guidelines on nomenclature. FASEB J. 1992 May;6(8):2512-3. PMID: https://www.ncbi.nlm.nih.gov/pubmed/1592203
- ↑ Wittinghofer A, Pai EF. The structure of Ras protein: a model for a universal molecular switch. Trends Biochem Sci. 1991 Oct;16(10):382-7. Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/1785141
- ↑ Moodie SA, Willumsen BM, Weber MJ, Wolfman A. Complexes of Ras.GTP with Raf-1 and mitogen-activated protein kinase kinase. Science. 1993 Jun 11;260(5114):1658-61. PMID: https://www.ncbi.nlm.nih.gov/pubmed/8503013
- ↑ 4.0 4.1 Boguski MS & McCormick F Proteins regulating Ras and its relative. Nature 366:643 1993 PMID: https://www.ncbi.nlm.nih.gov/pubmed/8259209
- ↑ 5.0 5.1 Sun H, Tonks NK, Bar-Sagi D. Inhibition of Ras-induced DNA synthesis by expression of the phosphatase MKP-1. Science. 1994 Oct 14;266(5183):285-8. PMID: https://www.ncbi.nlm.nih.gov/pubmed/7939666 [V12ras]