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Title
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The interaction of Ras with GTPase-activating proteins.
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Authors
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A.Wittinghofer,
K.Scheffzek,
M.R.Ahmadian.
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Ref.
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Febs Lett, 1997,
410,
63-67.
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PubMed id
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Abstract
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Ras plays a major role as a molecular switch in many signal transduction
pathways which lead to cell growth and differentiation. The GTPase reaction of
Ras is of central importance in the function of the switch since it terminates
Ras-effector interactions. GTPase-activating proteins (GAPs) accelerate the very
slow intrinsic hydrolysis reaction of the GTP-bound Ras by several orders of
magnitude and thereby act as presumably negative regulators of Ras action. The
GTP hydrolysis of oncogenic mutants of Ras remains unaltered. In this review we
discuss recent biochemical and structural findings relating to the mechanism of
GAP action, which strengthen the hypothesis that GAP accelerates the actual
cleavage step by stabilizing the transition state of the phosphoryl transfer
reaction.
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