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KMID : 0613820200300090826
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Journal of Life Science
2020 Volume.30 No. 9 p.826 ~ p.833
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Physiological Roles of Phospholipase Cγ and Its Mutations in Human Disease
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Jang Hyun-Jun
Choi Jang-Hyun
Chang Jong-Soo
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Abstract
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Phospholipase C gamma (PLCγ) has critical roles in receptor tyrosine kinase- and non-receptor tyrosine kinase-mediated cellular signaling relating to the hydrolysis of phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] to produce inositol 1,4,5 trisphosphate (IP3) and diacylglycerol (DAG), which promote protein kinase C (PKC) and Ca2+ signaling to their downstream cellular targets. PLCγ has two isozymes called PLCγ1 and PLCγ2, which control cell growth and differentiation. In addition to catalytically active X- and Y-domains, both isotypes contain two Src homology 2 (SH2) domains and an SH3 domain for protein?protein interaction when the cells are activated by ligand stimulation. PLCγ also contains two pleckstrin homology (PH) domains for membrane-associated phosphoinositide binding and protein-protein interactions. While PLCγ1 is widely expressed and appears to regulate intracellular signaling in many tissues, PLCγ2 expression is restricted to cells of hematopoietic systems and seems to play a role in the regulation of immune response. A distinct mechanism for PLCγ activation is linked to an increase in phosphorylation of specific tyrosine residue, Y783. Recent studies have demonstrated that PLCγ mutations are closely related to cancer, immune disease, and brain disorders. Our review focused on the physiological roles of PLCγ by means of its structure and enzyme activity and the pathological functions of PLCγ via mutational analysis obtained from various human diseases and PLCγ knockout mice.
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KEYWORD
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Disease-associated mutation, knockout mice, Phospholipase C gamma, structure
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