Identification and characterization of a new phospholipase C-like protein, PLC-L(2).
We have isolated a cDNA encoding a novel protein, PLC-L(2), with homology to the phospholipase C-like protein PLC-L and delta-type phospholipase C. PLC-L(2) contains a relatively well-conserved PH domain, PLC catalytic region, and X and Y domains. However, it did not have PLC activity. This inactivation was thought to be caused by the replacement of two amino acids that are essential for PLC activity, His356 and Tyr552, with Thr and Phe in the X and Y domain. PLC-L(2) has a wide distribution with strong expression in skeletal muscle and mapped to chromosome 3p24-25. The PH domain of PLC-L(2) bound strongly to PI(4,5)P(2) and Ins(1,4,5)P(3), and moderately to PI(4)P and PI(3,4,5)P(3). PLC-L(2) predominantly localized to perinuclear areas in both myoblast and myotube C2C12 cells. Ectopically expressed GFP-PLC-L(2) also mainly localized in perinuclear areas, including endoplasmic reticulum in COS 7 cells. Furthermore, the expression of GFP-PH showed the same intracellular distribution as the full-length PLC-L(2). All these results suggest that PLC-L(2) plays an important role in the regulation of Ins(1,4, 5)P(3) around the endoplasmic reticulum on which the Ins(1,4,5)P(3) receptor exists.
Otsuki
M
M
Department of Biochemistry, Institute of Medical Science, University of Tokyo, Japan.
Fukami
K
K
Kohno
T
T
Yokota
J
J
Takenawa
T
T
D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D001667:Binding, Competitive; D020134:Catalytic Domain; D002460:Cell Line; D002462:Cell Membrane / Q000737:chemistry; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics; D003001:Cloning, Molecular; D003593:Cytoplasm / Q000737:chemistry; D004721:Endoplasmic Reticulum / Q000737:chemistry; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins; D007527:Isoenzymes / Q000737:chemistry / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D018482:Muscle, Skeletal / Q000737:chemistry / Q000166:cytology; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000378:metabolism; D010740:Phospholipases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D020161:Physical Chromosome Mapping; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D017386:Sequence Homology, Amino Acid; D010738:Type C Phospholipases / Q000737:chemistry* / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D047908:Intracellular Signaling Peptides and Proteins; D007527:Isoenzymes; C530632:PLCL2 protein, human; D019269:Phosphatidylinositol 4,5-Diphosphate; C530633:Plcl2 protein, mouse; D012333:RNA, Messenger; D015544:Inositol 1,4,5-Trisphosphate; D010740:Phospholipases; D010738:Type C Phospholipases