Identification of a Protein Interacting with ras-p21- by Chemical Cross-Linking
There is accumulating evidence showing that ras oncogenes (Ha-ras, K-ras and N-ras) are involved in the processes of oncogenesis and cellular transformation1 . These genes encode highly homologous proteins of molecular weight 21 ,000 (p21) that are found in all mammalian tissues and are very conserved throughout evolution. ras-p21s are bound to the inner surface of the plasma membrane ; they bind GTP and GDP, and exhibit an intrinsic GTPase activity. A cytoplasmic protein of MW 110–120,000 has recently been identified by its capacity to enhance 100–500 fold the GTPase activity of ras-p21s (GAP) 2 ; it has been shown to interact with a domain of p21s necessary for their biological activity (amino acids 30–42 called “effector domain”) and may therefore constitute an effector of their physiological action3–6 . Point mutations resulting in the change of amino acids 12, 13, 59 or 61 have been shown to “activate” the oncogenic potential of ras oncogenes leading to cellular transformation. The GTPase activity of such mutant proteins is no longer activated by GAP, blocking them in a GTP-bound state that is thought to be the active form of p21s.
KeywordsGTPase Activity Intrinsic GTPase Activity Putative Effector Polyclonal Rabbit Serum Antiphosphotyrosine Antibody
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