1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase epsilon-1

Definition:

The production of the second messenger molecules diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) is mediated by activated phosphatidylinositol-specific phospholipase C enzymes. PLCE1 is a bifunctional enzyme which also regulates small GTPases of the Ras superfamily through its Ras guanine-exchange factor (RasGEF) activity. As an effector of heterotrimeric and small G-protein, it may play a role in cell survival, cell growth, actin organization and T-cell activation. In podocytes, is involved in the regulation of lamellipodia formation. Acts downstream of AVIL to allow ARP2/3 complex assembly.

References:

[1]. Jan Czyzyk, et al. Activation of CD4 T cells by Raf-independent effectors of Ras. Proc Natl Acad Sci U S A. 2003 May 13;100(10):6003-8. [Content Brief]

[2]. M Schmidt, et al. A new phospholipase-C-calcium signalling pathway mediated by cyclic AMP and a Rap GTPase. Nat Cell Biol. 2001 Nov;3(11):1020-4. [Content Brief]

[3]. Jia Rao, et al. Advillin acts upstream of phospholipase C ϵ1 in steroid-resistant nephrotic syndrome. J Clin Invest. 2017 Dec 1;127(12):4257-4269. [Content Brief]

[4]. T G Jin, et al. Role of the CDC25 homology domain of phospholipase Cepsilon in amplification of Rap1-dependent signaling. J Biol Chem. 2001 Aug 10;276(32):30301-7. [Content Brief]

[5]. Bernward Hinkes, et al. Positional cloning uncovers mutations in PLCE1 responsible for a nephrotic syndrome variant that may be reversible. Nat Genet. 2006 Dec;38(12):1397-405. [Content Brief]

[6]. I Lopez, et al. A novel bifunctional phospholipase c that is regulated by Galpha 12 and stimulates the Ras/mitogen-activated protein kinase pathway. J Biol Chem. 2001 Jan 26;276(4):2758-65. [Content Brief]

[7]. Aude S Ada-Nguema, et al. The small GTPase R-Ras regulates organization of actin and drives membrane protrusions through the activity of PLCepsilon. J Cell Sci. 2006 Apr 1;119(Pt 7):1307-19. [Content Brief]

[8]. Sandrine Evellin, et al. Stimulation of phospholipase C-epsilon by the M3 muscarinic acetylcholine receptor mediated by cyclic AMP and the GTPase Rap2B. J Biol Chem. 2002 May 10;277(19):16805-13. [Content Brief]

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