1-phosphatidylinositol-4,5-bisphosphate phosphodiesterase epsilon 1 (phospholipase C-epsilon-1, PLC-epsilon-1, phosphoinositide-specific phospholipase C epsilon-1, pancreas-enriched phospholipase C, PLCE1, KIAA1516, PLCE, PPLC)
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Function
- phospholipase C, mediates production of 2nd messengers diacylglycerol & IP3
- bifunctional enzyme, also regulates small GTPases of Ras superfamily through its RasGEF activity
- role in cell survival, cell growth, actin organization & T-cell activation
- activated by heterotrimeric G-protein subunits GNA12, GNA13 & GNB1-GNG2
- activated by HRAS, RAP1A, RHOA, RHOB, RHOC, RRAS & RRAS2
- activated by the Gs-coupled *GPCRs ADRB2, PTGER1 & CHRM3 through cyclic-AMP formation & RAP2B activation
- inhibited by Gi-coupled GPCRs
- interacts with RHOA. HRAS, RAP1A, RAP2A, RAP2B & RRAS
* GPCR = G protein-coupled receptor
1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate + H2O
<-->
1D-myo-inositol 1,4,5-trisphosphate + diacylglycerol
Structure
- contains 1 C2 domain
- contains 1 PI-PLC X-box domain
- contains 1 PI-PLC Y-box domain
- contains 2 Ras-associating domains
- contains 1 Ras-GEF domain
- Ras-GEF domain has a GEF activity towards HRAS & RAP1A
- mediates activation of the mitogen-activated protein kinase pathway.
Compartment
- cytoplasm; cytosol
- recruited to plasma membrane by activated HRAS & RAP2
- recruited to perinuclear membrane by activated RAP1A
- isoforms 1 & 2 associate with Golgi membranes
Alternative splicing
named isoforms=2
Expression
- widely expressed
- isoform 1 is broadly expressed & only absent in
- isoform 2 is specifically expressed in placenta, lung & spleen
Pathology
- overexpressed during heart failure