Nucleotide regulatory protein-mediated activation of polyphosphoinositide-specific phospholipase C is inhibited by protein kinase C
Exposure of human polymorphonuclear leukocytes (PMNs) to chemoattractants results in the rapid production of inositol trisphosphate (IP/sub 3/) by the phosphodiesteric cleavage of phosphatidylinositol 4,5-bisphosphate (PIP/sub 2/). Receptor occupancy is coupled to phospholipase C activation by a nucleotide regulatory (N) protein. Incubation of PMNs with phorbol myristate acetate (PMA) inhibits chemoattractant-induced IP/sub 3/ production, but potentiates IP/sub 3/ production by Concanavalin A which activates phospholipase C by an N protein-independent mechanism. Plasma membranes prepared from control or PMA-treated PMNs demonstrate equivalent chemoattractant-induced binding of GTP/sub ..gamma../(/sup 35/S), indicating that receptor-N protein interactions remain unlayered by the PMA treatment. In contrast to those from control PMNs, membranes isolated from PMA-treated cells do not degrade PIP/sub 2/ upon incubation with GTP/sub ..gamma../S at low concentrations of Ca/sup 2 +/. These membranes however do degrade PIP/sub 2/ in the presence of 1 mM Ca/sup 2 +/, indicating that treatment with PMA does not directly inactivate the phospholipase. Incubation of PMNs with phorbol dibutyrate, which also activates protein kinase C, but not an inactive ester, 4-..cap alpha..-phorbol didecanoate, causes a similar loss of the ability of the N protein to activate PIP/sub 2/ hydrolysis. Therefore, the mechanism of PMA-induced attenuation of receptor-mediated PIP/sub 2/ breakdown appears to involve a protein kinase C-catalyzed reaction which prevents coupling of the activated N protein to phospholipase C.
- Research Organization:
- Duke Univ. Medical Center, Durham, NC
- OSTI ID:
- 5233983
- Report Number(s):
- CONF-8606151-; TRN: 86-031414
- Journal Information:
- Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States), Vol. 45:6; Conference: 76. annual meeting of the Federation of American Society for Experimental Biology, Washington, DC, USA, 8 Jun 1986
- Country of Publication:
- United States
- Language:
- English
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550201* - Biochemistry- Tracer Techniques