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