Subcellular localization and PKC-dependent regulation of the human lysophospholipase A/acyl-protein thioesterase in WISH cells.
Lysophospholipases play essential roles in keeping their multi-functional substrates, the lysophospholipids, at safe levels. Recently, a 25 kDa human lysophospholipase A (hLysoPLA I) that is highly conserved among rat, mouse, human and rabbit has been cloned, expressed and characterized and appears to hydrolyze only lysophospholipids among the various lipid substrates. Interestingly, this enzyme also displays acyl-protein thioesterase activity towards a G protein alpha subunit. To target the subcellular location of this hLysoPLA I, we have carried out immunocytochemical studies and report here that hLysoPLA I appears to be associated with the endoplasmic reticulum (ER) and nuclear envelope in human amnionic WISH cells and not the plasma membrane. In addition, we found that the hLysoPLA I can be up-regulated by phorbol 12-myristate 13-acetate (PMA) stimulation, a process in which phospholipase A(2) is activated and lysophospholipids are generated in WISH cells. Furthermore, the PMA-induced hLysoPLA I expression can be blocked by the protein kinase C (PKC) inhibitor Gö6976. The regulated expression of the LysoPLA/acyl-protein thioesterase by PKC may have important implications for signal transduction processes.
Wang
A
A
Department of Chemistry and Biochemistry, University of California at San Diego, La Jolla, CA 92093-0601, USA.
Johnson
C A
CA
Jones
Y
Y
Ellisman
M H
MH
Dennis
E A
EA
D002460:Cell Line; D004721:Endoplasmic Reticulum / Q000201:enzymology; D004789:Enzyme Activation; D006801:Humans; D007150:Immunohistochemistry; D008245:Lysophospholipase / Q000032:analysis / Q000145:classification / Q000378:metabolism*; D008246:Lysophospholipids / Q000378:metabolism; D009685:Nuclear Envelope / Q000201:enzymology; D010170:Palmitoyl-CoA Hydrolase; D011493:Protein Kinase C / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate; D013869:Thiolester Hydrolases / Q000378:metabolism*; D015854:Up-Regulation
D008246:Lysophospholipids; D011493:Protein Kinase C; D008245:Lysophospholipase; D013869:Thiolester Hydrolases; C106353:ACOT8 protein, human; D010170:Palmitoyl-CoA Hydrolase; D013755:Tetradecanoylphorbol Acetate