Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
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Drug
Enzyme
Compound
Query: EC:2.7.11.1 (
protein kinase
)
81,284
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
The Ras-like guanine-nucleotide-binding protein Rap1 controls integrin alpha(IIb)beta3 activity and platelet aggregation. Recently, we have found that Rap1 activation can be blocked by the nitric oxide/cyclic guanosine monophosphate (NO/cGMP) signaling pathway by type 1
cGMP-dependent protein kinase
(
cGKI
). In search of possible targets of NO/cGMP/
cGKI
, we studied the expression of Rap1-specific GTPase-activating proteins (GAPs) and guanine nucleotide exchange factors (GEFs) in platelets. We could detect mRNAs for a new protein most closely related to Rap1GAP and for postsynaptic density-95 discs-large and zona occludens protein 1 (PDZ)-GEF1 and CalDAG-GEFs I and III. Using 5'-rapid amplification of cDNA ends (RACE), we isolated the complete cDNA of the new GAP encoding a 715-amino acid protein, which we have termed
Rap1GAP2
.
Rap1GAP2
is expressed in at least 3 splice variants, 2 of which are detectable in platelets. Endogenous
Rap1GAP2
protein partially colocalizes with Rap1 in human platelets. In transfected cells, we show that
Rap1GAP2
exhibits strong GTPase-stimulating activity toward Rap1.
Rap1GAP2
is highly phosphorylated, and we have identified
cGKI
as a
Rap1GAP2
kinase.
cGKI
phosphorylates
Rap1GAP2
exclusively on serine 7, a residue present only in the platelet splice variants of
Rap1GAP2
. Phosphorylation of
Rap1GAP2
by
cGKI
might mediate inhibitory effects of NO/cGMP on Rap1.
Rap1GAP2
is the first GTPase-activating protein of Rap1 found in platelets and is likely to have an important regulatory role in platelet aggregation.
...
PMID:Rap1GAP2 is a new GTPase-activating protein of Rap1 expressed in human platelets. 1563 3
