PubMed Journals: Cell Death Differ

  Source:		PMID: 10200531

    		Cell Death Differ. 1998 Sep;5(9):729-34.
			Proteolytic cleavage of ras GTPase-activating
			protein during apoptosis.

			Wen LP(1), Madani K, Martin GA, Rosen GD.

			Author Information
			(1) Department of Pulmonary and Critical
			Care Medicine, Stanford University, Stanford,
			California 94305-5236, USA.

			p120-ras GTPase-activating protein (rasGAP)
			associates with Ras and negatively regulates
			Ras signaling by stimulating the intrinsic
			rate of Ras GTPase activity. rasGAP also
			associates with other cellular signaling
			proteins which suggest that rasGAP may play
			a role in coordinating other signal transduction
			pathways. Disruption of rasGAP in vivo results
			in extensive apoptosis. Fas-mediated apoptosis
			results in the activation of caspases that
			cleave cellular substrates which are important
			for maintaining cytoplasmic and nuclear
			integrity. We show here that rasGAP is
			proteolytically cleaved by caspases early
			in Fas-induced apoptosis of Jurkat cells.
			rasGAP was also cleaved by DNA-damaging chemotherapeutic
			agents and TNF-related apoptosis inducing ligand
			(TRAIL), also known as Apo2L. Based on the size
			of the products generated by cleavage of
			deletion mutants of rasGAP we predict that
			cleavage of rasGAP occurs in the hydrophobic
			region and between the SH2(2) and ras-p21
			interacting domain which would leave an
			intact ras-p21 interacting domain. Interestingly,
			cleavage of rasGAP in vitro enhanced rasGAP
			hydrolysis activity. Our results demonstrate
			that diverse apoptotic stimuli cause
			caspase-mediated cleavage of rasGAP early
			in apoptosis.

			DOI: 10.1038/sj.cdd.4400409 PMID: 10200531
			[Indexed for MEDLINE]

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