Activation of Phospholipase C-γ by the Concerted Action of Tau Proteins and Arachidonic Acid

doi:10.1074/jbc.271.31.18342

Activation of Phospholipase C-γ by the Concerted Action of Tau Proteins and Arachidonic Acid*

From the Laboratory of Cell Signaling, NHLBI, National Institutes of Health, Bethesda, Maryland 20892

^¶ To whom correspondence should be addressed:
National Institutes of Health, Bldg. 3, Rm. 122, 3 Center Dr. MSC 0320, Bethesda, MD 20892-0320.
Tel.: 301-496-9646; Fax: 301-496-0599.

↵^‡ Present address: Dept. of Internal Medicine, College of Medicine, Ajou University, Suwon, Korea.
↵^§ Present address: College of Home Economics, Chonnam University, Kwangju, Korea.

Abstract

Phospholipase C-γ (PLC-γ) isozymes are thought to be activated by receptor-induced tyrosine phosphorylation. Proteins that activate PLC-γ1 have now been purified from bovine brain and identified as members of the tau family of microtubule-associated proteins. Activation of PLC-γ by tau was enhanced in the presence of unsaturated fatty acids such as arachidonic acid, saturated fatty acids being ineffective. Maximal (15-20-fold) activation was apparent in the presence of 0.15 μM tau and 25 μM arachidonic acid (AA). The effect of tau and AA was specific to PLC-γ isozymes in the presence of submicromolar concentrations of Ca²⁺ and was markedly inhibited by phosphatidylcholine. These results suggest that in cells that express tau, receptors coupled to cytosolic phospholipase A₂ may activate PLC-γ isozymes indirectly in the absence of tyrosine phosphorylation through the hydrolysis of phosphatidylcholine to generate AA.

Footnotes

↵* The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
↵¹ The abbreviations used are:

PIP₂

phosphatidylinositol 4,5-bisphosphate

PLC

phospholipase C

IP₃

inositol 1,4,5-trisphosphate

PI

phosphatidylinositol

AA

arachidonic acid

PLA₂

phospholipase A₂

PS

phosphatidylserine

PE

phosphatidylethanolamine

PC

phosphatidylcholine

DTT

dithiothreitol

HPLC

high pressure liquid chromatography

PAGE

polyacrylamide gel electrophoresis

cPLA₂

cytosolic PLA₂

PH

pleckstrin homology.
↵² S. C. Hwang, D.-Y. Jhon, Y. S. Bae, J. H. Kim, and S. G. Rhee, unpublished data.
- Received April 2, 1996.
- Revision received May 7, 1996.