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ras proto-oncogene protein (p21ras)

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: a) GTPase-activating proteins b) guanine nucleotide exchange factors Genetics: - 4 subtypes are 'true' ras proteins [4] - p21ras subtypes encoded by separate genes; sequence variability resides in carboxy terminus Pathology: - the oncogenic protein V12ras in which Gly-12 is mutated to Val results in a protein locked in its GTP-bound form [5]. Note: 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.

Interactions

molecular events

Related

FXYD domain-containing ion transport regulator 3 (Cl- conductance inducer protein Mat-8, mammary tumor 8 kD protein, phospholemman-like, FXYD3, MAT8, PLML) ras proto-oncogene ras signal transduction

Specific

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)

General

ras subfamily protein

Properties

SIZE: MW = 21 kD COMPARTMENT: plasma membrane CELL: unspecified cell type ORGANISM: mammal MOTIF: binding site FOR-BINDING-OF: raf1 proto-oncogene protein binding site FOR-BINDING-OF: ras GTPase activator protein P-loop FOR-BINDING-OF: guanosine triphosphate guanosine diphosphate CaaX motif SITE: C-TERMINUS QUALITIES: AAX-TRUNCATED CARBOXYMETHYLATED EFFECTOR-BOUND: farnesyl BOUND-VIA: cysteine residue MISC-INFO: INHIBITOR = RAS_GAP

References

  1. 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: 1592203
  2. 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: 1785141
  3. 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: 8503013
  4. Boguski MS & McCormick F Proteins regulating Ras and its relative. Nature 366:643 1993 PMID: 8259209
  5. 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: 7939666 [V12ras]

Component-of

molecular complex