|
Function
Phospholipase C (PLC) or 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma cleaves phospholipids before the phosphate group. PLCs catalyze the conversion of phosphatidylinositol 4,5-bisphosphate to inositol 1,4,5-trisphosphate and diacylglycerol.[1]
- Phospholipase C β is a key enzyme in mammalian taste signal transduction[2]. For more details on phospholipase C β see PLC beta 3 Gq.
- Phospholipase C γ is a physiological guanine nucleotide exchange factor for the nuclear GTPase[3].
- Phospholipase C δ is critical for Ca+2 homeostasis.
- Phospholipase C ε is an effector for Ras.
- Phosphatidylinositol-specific phospholipase C (PIPLC) catalyzes the hydrolysis of phosphatidylinositol into inositol triphosphate and deacylglycerol. PIPLC functions at the plasma membrane. PIPLC can release phosphatidylinositol-linked proteins (i.e., acetylcholinesterase) from the membrane by enzymatically cleaving their GPI anchor. [4]. See also IP3 is second messenger.
Disease
Phospholipase C γ gene blocking can stop breast cancer.[5] Phospholipase C δ has important suppressive role in the development and progression of esophageal carcinoma. Mutations in phospholipase C δ1 cause hereditary leukonychia[6]. Mutations in phospholipase C ε1 are associated with stomach cancer risk and nephrotic syndromes[7].
Structural highlights
The active site of PIPLC is located at a solvent-accessible cleft at the C-terminal.[8] Solvent-accessible cleft.
- ↑ Barr AJ, Marjoram R, Xu J, Snyderman R. Phospholipase C-beta 2 interacts with mitogen-activated protein kinase kinase 3. Biochem Biophys Res Commun. 2002 Apr 26;293(1):647-52. PMID:12054652 doi:https://dx.doi.org/10.1016/S0006-291X(02)00259-0
- ↑ Yasuoka A, Aihara Y, Matsumoto I, Abe K. Phospholipase C-beta 2 as a mammalian taste signaling marker is expressed in the multiple gustatory tissues of medaka fish, Oryzias latipes. Mech Dev. 2004 Jul;121(7-8):985-9. PMID:15210203 doi:https://dx.doi.org/10.1016/j.mod.2004.03.009
- ↑ Ye K, Aghdasi B, Luo HR, Moriarity JL, Wu FY, Hong JJ, Hurt KJ, Bae SS, Suh PG, Snyder SH. Phospholipase C gamma 1 is a physiological guanine nucleotide exchange factor for the nuclear GTPase PIKE. Nature. 2002 Jan 31;415(6871):541-4. PMID:11823862 doi:https://dx.doi.org/10.1038/415541a
- ↑ Mortara RA, Minelli LM, Vandekerckhove F, Nussenzweig V, Ramalho-Pinto FJ. Phosphatidylinositol-specific phospholipase C (PI-PLC) cleavage of GPI-anchored surface molecules of Trypanosoma cruzi triggers in vitro morphological reorganization of trypomastigotes. J Eukaryot Microbiol. 2001 Jan-Feb;48(1):27-37. PMID:11249190
- ↑ Sala G, Dituri F, Raimondi C, Previdi S, Maffucci T, Mazzoletti M, Rossi C, Iezzi M, Lattanzio R, Piantelli M, Iacobelli S, Broggini M, Falasca M. Phospholipase Cgamma1 is required for metastasis development and progression. Cancer Res. 2008 Dec 15;68(24):10187-96. doi: 10.1158/0008-5472.CAN-08-1181. PMID:19074886 doi:https://dx.doi.org/10.1158/0008-5472.CAN-08-1181
- ↑ Mir H, Khan S, Arif MS, Ali G, Wali A, Ansar M, Ahmad W. Mutations in the gene phospholipase C, delta-1 (PLCD1) underlying hereditary leukonychia. Eur J Dermatol. 2012 Nov-Dec;22(6):736-9. doi: 10.1684/ejd.2012.1852. PMID:23149345 doi:https://dx.doi.org/10.1684/ejd.2012.1852
- ↑ . Editorial: The glue-ear syndrome. Lancet. 1975 Aug 30;2(7931):397-8. PMID:51196
- ↑ Heinz DW, Ryan M, Bullock TL, Griffith OH. Crystal structure of the phosphatidylinositol-specific phospholipase C from Bacillus cereus in complex with myo-inositol. EMBO J. 1995 Aug 15;14(16):3855-63. PMID:7664726
|
