Mechanism of protein kinase C activation by phosphatidylinositol 4,5-bisphosphate
- Duke Univ., Durham, NC (USA)
The mechanism of protein kinase C (PKC) activation by phosphatidylinositol 4,5-bisphosphate (PIP{sub 2}), phosphatidylinositol 4-monophosphate (PIP), and phosphatidylinositol (PI) was investigated by using Triton X-100 mixed micellar methods. The activation of PKC by PIP{sub 2}, for which maximal activity was 60% of that elicited by sn-1,2-diacylglycerol (DAG), was similar to activation by DAG in several respects: (1) activation by PIP{sub 2} and DAG required phosphatidylserine (PS) as a phospholipid cofactor, (2) PIP{sub 2} and DAG reduced the concentration of Ca{sup 2+} and PS required for activation, (3) the concentration dependences of activation by PIP{sub 2} and DAG depended on the concentration of PS, and (4) PIP{sub 2} and DAG complemented one another to achieve maximal activation. On the other hand, PIP{sub 2} activation of the PKC differed from activation by DAG in several respects. With increasing concentrations of PIP{sub 2}, (1) the optimal concentration of PS required was constant at 12 mol%, (2) the maximal activity at 12 mol% PS increased, and (3) the cooperativity for PS decreased. PIP{sub 2} did not inhibit ({sup 3}H)phorbol 12,13-dibutyrate (PDBu) binding of PKC at saturating levels of PS; however, at subsaturating levels of PS, PIP{sub 2} enhanced ({sup 3}H)PDBu binding by acting as a phospholipid cofactor. PIP did not function as an activator but served as a phospholipid cofactor in the presence of PS. These data establish that PIP{sub 2}, PIP, and PI can function to spare, in part, the PS phospholipid cofactor requirement of PKC, and they demonstrate that PIP{sub 2} but not PIP and PI can function as a lipid activator of PKC by mechanisms distinct from those of DAG and phorbol esters.
- OSTI ID:
- 5557648
- Journal Information:
- Biochemistry; (United States), Vol. 30:4; ISSN 0006-2960
- Country of Publication:
- United States
- Language:
- English
Similar Records
Monoclonal antibodies against type II rat brain protein kinase
Structure-activity relationship of synthetic branched-chain distearoylglycerol (distearin) as protein kinase C activators
Related Subjects
PHOSPHOLIPIDS
BIOCHEMISTRY
PHOSPHOTRANSFERASES
CHEMICAL ACTIVATION
BRAIN
LABELLED COMPOUNDS
LIPIDS
MICELLAR SYSTEMS
PHORBOL ESTERS
PHOSPHORUS 32
TRITIUM COMPOUNDS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BODY
CARCINOGENS
CENTRAL NERVOUS SYSTEM
CHEMISTRY
DAYS LIVING RADIOISOTOPES
ENZYMES
ESTERS
HYDROGEN COMPOUNDS
ISOTOPES
LIGHT NUCLEI
NERVOUS SYSTEM
NUCLEI
ODD-ODD NUCLEI
ORGANIC COMPOUNDS
ORGANIC PHOSPHORUS COMPOUNDS
ORGANS
PHOSPHORUS ISOTOPES
PHOSPHORUS-GROUP TRANSFERASES
RADIOISOTOPES
TRANSFERASES
550201* - Biochemistry- Tracer Techniques