Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
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Target Concepts:
Gene/Protein
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Enzyme
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Query: EC:3.1.4.3 (
phospholipase C
)
18,461
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Mammalian Ras proteins regulate multiple effectors including Raf,
Ral guanine nucleotide dissociation stimulator
(
RalGDS
), and phosphoinositide 3-kinase. In the nematode Caenorhabditis elegans, LIN-45 Raf has been identified by genetic analyses as an effector of LET-60 Ras. To search for other effectors in C. elegans, we performed a yeast two-hybrid screening for LET-60-binding proteins. The screening identified two cDNA clones encoding a phosphoinositide-specific
phospholipase C
(PI-PLC) with a predicted molecular mass of 210 kDa, designated PLC210. PLC210 possesses two additional functional domains unseen in any known PI-PLCs. One is the C-terminal Ras-associating domain bearing a structural homology with those of
RalGDS
and AF-6. This domain, which could be narrowed down to 100 amino acid residues, associated in vitro with human Ha-Ras in a GTP-dependent manner and competed with yeast adenylyl cyclase for binding Ha-Ras. The binding was abolished by specific mutations within the effector region of Ha-Ras. The other functional domain is the N-terminal CDC25-like domain, which possesses a structural homology to guanine nucleotide exchange proteins for Ras. These results strongly suggest that PLC210 belongs to a novel class of PI-PLC, which is a putative effector of Ras.
...
PMID:Identification of PLC210, a Caenorhabditis elegans phospholipase C, as a putative effector of Ras. 949 45
The angiotensin II type 1 receptor (AT(1)R) plays an important role in cardiovascular function and as such represents a primary target for therapeutic intervention. The AT(1)R has traditionally been considered to be coupled to the activation of
phospholipase C
(
PLC
) beta via its association with G alpha(q/11), leading to increases in intracellular inositol phosphate (IP) and release of calcium from intracellular stores. In the present study, we investigated whether the small GTPase RalA contributed to the regulation of AT(1)R endocytosis and signaling. We find that neither RalA nor RalB is required for the endocytosis of the AT(1)R, but that RalA expression is required for AT(1)R-stimulated IP formation but not 5-HT(2A) receptor-mediated IP formation. AT(1)R-activated IP formation is lost in the absence of
Ral guanine nucleotide dissociation stimulator
(
RalGDS
), and requires the beta-arrestin-dependent plasma membrane translocation of
RalGDS
. G alpha(q/11) small interfering RNA (siRNA) treatment also significantly attenuates both AT(1)R- and 5-HT(2A) receptor-stimulated IP formation after 30 min of agonist stimulation.
PLC
-delta1 has been reported to be activated by RalA, and we show that AT(1)R-stimulated IP formation is attenuated after
PLC
-delta 1 siRNA treatment. Taken together, our results provide evidence for a G protein-coupled recepto-activated and
RalGDS
/Ral-mediated mechanism for
PLC
-delta 1 stimulation.
...
PMID:The small GTPase Ral couples the angiotensin II type 1 receptor to the activation of phospholipase C-delta 1. 2001 11
