Multiple roles of phosphoinositide-specific phospholipase C isozymes.
Phosphoinositide-specific phospholipase C is an effector molecule in the signal transduction process. It generates two second messengers, inositol-1,4,5-trisphosphate and diacylglycerol from phosphatidylinositol 4,5-bisphosphate. Currently, thirteen mammal PLC isozymes have been identified, and they are divided into six groups: PLC-beta, -gamma, -delta, -epsilon, -zeta and -eta. Sequence analysis studies demonstrated that each isozyme has more than one alternative splicing variant. PLC isozymes contain the X and Y domains that are responsible for catalytic activity. Several other domains including the PH domain, the C2 domain and EF hand motifs are involved in various biological functions of PLC isozymes as signaling proteins. The distribution of PLC isozymes is tissue and organ specific. Recent studies on isolated cells and knockout mice depleted of PLC isozymes have revealed their distinct phenotypes. Given the specificity in distribution and cellular localization, it is clear that each PLC isozyme bears a unique function in the modulation of physiological responses. In this review, we discuss the structural organization, enzymatic properties and molecular diversity of PLC splicing variants and study functional and physiological roles of each isozyme.
Suh
Pann-Ghill
PG
Division of Molecular and Life Sciences, Pohang University of Science and Technology, Pohang, Korea. pgs@postech.ac.kr
Park
Jae-Il
JI
Manzoli
Lucia
L
Cocco
Lucio
L
Peak
Joanna C
JC
Katan
Matilda
M
Fukami
Kiyoko
K
Kataoka
Tohru
T
Yun
Sanguk
S
Ryu
Sung Ho
SH
D017398:Alternative Splicing; D000818:Animals; D020134:Catalytic Domain; D006801:Humans; D007527:Isoenzymes / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D054801:Phosphoinositide Phospholipase C / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
D007527:Isoenzymes; D054801:Phosphoinositide Phospholipase C