Nucleotide regulatory protein-mediated activation of polyphosphoinositide-specific phospholipase C is inhibited by protein kinase C

Conference · Thu May 01 04:00:00 EDT 1986 · Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States)

OSTI ID:5233983

Smith, C D; Snyderman, R

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-
• Conference Information: Journal Name: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States) Journal Volume: 45:6
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ALKALINE EARTH METAL COMPOUNDS
ANIMALS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOLOGICAL EFFECTS
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BODY FLUIDS
CALCIUM COMPOUNDS
CARBOHYDRATES
CARBOXYLESTERASES
CARCINOGENS
CELL CONSTITUENTS
CELL MEMBRANES
DAYS LIVING RADIOISOTOPES
ENZYME ACTIVITY
ENZYMES
ESTERASES
ESTERS
EVEN-ODD NUCLEI
HYDROLASES
INOSITOL
INOSITOLS
ISOTOPE APPLICATIONS
ISOTOPES
LEUKOCYTES
LIGHT NUCLEI
LIPASE
MAMMALS
MAN
MATERIALS
MEMBRANE PROTEINS
MEMBRANES
METABOLISM
MONOSACCHARIDES
NUCLEI
ORGANIC COMPOUNDS
OXYGEN COMPOUNDS
PHORBOL ESTERS
PHOSPHATES
PHOSPHODIESTERASES
PHOSPHORUS COMPOUNDS
PHOSPHORUS-GROUP TRANSFERASES
PHOSPHOTRANSFERASES
PRIMATES
PROTEINS
RADIOISOTOPES
RECEPTORS
SACCHARIDES
SULFUR 35
SULFUR ISOTOPES
TRACER TECHNIQUES
TRANSFERASES
VERTEBRATES