Cytosolic Phospholipase A2a Interacts With Microtubules
Cytosolic phospholipase A2 (cPLA2) a plays crucial roles in the lipid mediator-biosynthetic pathway following cell activationl. Submicromolar concentrations of Ca2+ are required for cPLA2a to exert its catalytic activity, and this enzyme preferentially hydrolyses phospholipids bearing arachidonic acid2. cPLA2a exists in most mammalian cells, and its activation is regulated by several postreceptor signal transduction events, such as Ca2+ mobilization3, phosphorylation4,5, and gene induction6. Upon Ca2+mobilizing stimulation, cPLA2a translocates rapidly to the perinuclear area7-9. cPLA2a has several functionally distinct regions: an amino-terminal Ca2+-dependent lipid-binding domain (amino acids 18-138) called the C2 domainl0, a carboxy-terminal region (amino acids 179-749) containing the catalytic domain, a putative pleckstrin homology domain 11, and two critical serine residues (Ser505 and Ser727), which undergo activation-directed phosphorylation12. We recently demonstrated that the C2 domain of cPLA2 interacts with vimentin, a major component of intermeiate filaments, in a Ca2+dependent mannerl3. In this report, we have found that another cytoskeletal protein in the cytosol of fibroblasts binds to the C2 domain of cPLA2a.
KeywordsIntermediate Filament Microtubule Assembly Arachidonic Acid Release Cytosolic Phospholipase Perinuclear Area
Unable to display preview. Download preview PDF.
- 1.M. Murakami, Y. Nakatani, G. Atsumi, K. Inoue, and I. Kudo, Regulatory functions of phospholipase A2, Crit. Rev. Immunol. 17: 225–283 (1997)Google Scholar
- 6.L.-L. Lin, A. Y. Lin, and D. L. DeWitt, Interleukin-1 alpha induces the accumulation of cytosolic phospholipase A2 and the release of prostaglandin E2 in human fibroblasts, J. Biol. Chem. 267: 2345–23454 (1992)Google Scholar
- 12.A. G. Borsch-haubold, F. Bartoli, J. Asselin, T. Dudler, R. M. Kramer, R. Apitz-Castro, S. P. Watson, and M. H. Gelb, Identification of the phosphorylation sites of cytosolic phospholipase A2 in agoniststimulated human platelets and HeLa cells, J. Biol. Chem. 273: 4449–4458 (1998)PubMedCrossRefGoogle Scholar