Mammalian Phospholipase C

Abstract

Phospholipase C (PLC) converts phosphatidylinositol 4,5-bisphosphate (PIP(2)) to inositol 1,4,5-trisphosphate (IP(3)) and diacylglycerol (DAG). DAG and IP(3) each control diverse cellular processes and are also substrates for synthesis of other important signaling molecules. PLC is thus central to many important interlocking regulatory networks. Mammals express six families of PLCs, each with both unique and overlapping controls over expression and subcellular distribution. Each PLC also responds acutely to its own spectrum of activators that includes heterotrimeric G protein subunits, protein tyrosine kinases, small G proteins, Ca(2+), and phospholipids. Mammalian PLCs are autoinhibited by a region in the catalytic TIM barrel domain that is the target of much of their acute regulation. In combination, the PLCs act as a signaling nexus that integrates numerous signaling inputs, critically governs PIP(2) levels, and regulates production of important second messengers to determine cell behavior over the millisecond to hour timescale.

G-protein-coupled receptor controls steroid hormone signaling in cell membrane

“…20E via GPCR-, PLC-, Ca 21 -, and PKC-signaling mediates USP1 phosphorylation for gene transcription 12 . At the downstream of ligand activated-GPCR, PLC hydrolyzes phosphatidylinositol 4,5-bisphosphate to generate inositol 1,4,5-triphosphate (IP3) and diacylglycerol (DAG) 37 . IP3 binds to its receptor in the endoplasmic reticulum membrane to drive the release of intracellular calcium ions, whereas DAG and Ca 21 bind to the protein kinase C (PKC) to activate PKC 38 .…”

Cool-temperature-mediated activation of phospholipase C-γ 2 in the human hereditary disease PLAID

“…Inositol-phospholipid-specific phospholipases C (PLCs) catalyse the formation of inositol 1,4,5-trisphosphate and diacylglycerol, and, at the same time, decrease the local or general plasma membrane abundance of their substrate, phosphatidylinositol 4,5-bisphosphate (PtdInsP 2 ) [1]. The latter three molecules are important mediators of cellular signaling.…”

Dysfunction of phospholipase Cγ in immune disorders and cancer

“…Different aspects of PLC-mediated signalling have been covered in a number of excellent reviews that focus, for example, on the catalytic mechanism [7], regulatory interactions and physiological roles of PLC families [1][2][3][4][5] or on structural and mechanistic aspects of regulation [8][9][10]. In this review, we highlight recent experimental evidence related to the dysfunction of PLCγ enzymes and links to disease, based on genetic and genomic analysis of animal models and patients; we further discuss the molecular mechanisms that underpin dysfunction.…”