Gene/Protein
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Enzyme
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Pivot Concepts:
Gene/Protein
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Target Concepts:
Gene/Protein
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Query: UNIPROT:P42574 (
caspase-3
)
45,978
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Caspases are proteases involved in various physiological and pathological processes in the nervous system, including development and pathogenesis.
GRASP-1
is a recently identified neuronal substrate of
caspase-3
-subfamily caspases. It is a Ras-guanine nucleotide exchange factor (RasGEF) that interacts with the glutamate receptor interacting protein (GRIP). This alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptor/GRIP protein complex has been proposed to be involved in AMPA receptor synaptic targeting. The
caspase-3
cleavage of
GRASP-1
separates the N-terminal RasGEF catalytic domain from the C-terminal GRIP-interacting region, potentially disrupting regulation of the RasGEF activity by GRIP. To examine the regulation and regional distribution of the
caspase-3
cleavage of
GRASP-1
in vivo, we generated a cleavage site-specific antibody, termed CGP, against the cleaved N-terminal fragment of
GRASP-1
. Using this antibody, we have examined the caspase cleavage of
GRASP-1
during postnatal development and following ischemia in mice. We found that caspase cleavage of
GRASP-1
occurs in specific brain regions in a time-dependent manner during development and ischemia. This data provides an important account of the brain areas that might require
caspase-3
activity in postnatal development and ischemic damage, which has not been documented. It also demonstrates that the CGP antibody is a powerful tool for studying neuronal activity of the
caspase-3
-subfamily caspases in vivo.
...
PMID:Physiological and pathological caspase cleavage of the neuronal RasGEF GRASP-1 as detected using a cleavage site-specific antibody. 1220 67
GRASP-1
is a neuronally enriched protein that interacts with the AMPA-type glutamate receptor/GRIP complex.
GRASP-1
can be cleaved by
Caspase-3
in both normal and ischemic brains although the functional significance of this cleavage remains elusive. We investigated signal transduction pathways that might lie downstream of
GRASP-1
and found that
GRASP-1
potently activates JNK pathway signaling, with no effect on ERK signaling. Such JNK pathway activating activity requires binding of
GRASP-1
to both JNK and the upstream JNK pathway activator MEKK-1. Furthermore, mutations that prevent Caspase 3-cleavage of
GRASP-1
dramatically inhibit the JNK pathway activating activity of
GRASP-1
, suggesting a novel link between
Caspase-3
activation and JNK pathway signaling. These results suggest that
GRASP-1
serves as a scaffold protein to facilitate MEKK-1 activation of JNK signaling in neurons.
...
PMID:GRASP-1 is a neuronal scaffold protein for the JNK signaling pathway. 1776 Nov 73
