Insulin induced phosphorylation and activation of the cGMP-inhibited cAMP phosphodiesterase in human platelets.
Insulin induced phosphorylation and activation of the cGMP inhibited cAMP phosphodiesterase (cGI-PDE) in human platelets were demonstrated after isolation of the enzyme with specific polyclonal cGI-PDE antibodies. The demonstration of this insulin effect required suppression of basal cGI-PDE phosphorylation, through the use of the protein kinase inhibitor H-7 (1-(5-isoquinolinylsulfonyl)-2-methylpiperazine). The human platelet insulin receptor beta-subunit, previously identified as a 97 kDa polypeptide, was detected with the use of wheat germ agglutinin chromatography and anti-phosphotyrosine antibodies. These results suggest that insulin, through phosphorylation/activation of cGI-PDE, could decrease cAMP/cAMP dependent protein kinase (cAMP-PK) activity and thereby make the platelets more sensitive towards aggregating agents.
López-Aparicio
P
P
Department of Medical and Physiological Chemistry, University of Lund, Sweden.
Rascón
A
A
Manganiello
V C
VC
Andersson
K E
KE
Belfrage
P
P
Degerman
E
E
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000097:blood* / Q000302:isolation & purification; D006152:Cyclic GMP / Q000494:pharmacology*; D004591:Electrophoresis, Polyacrylamide Gel; D004789:Enzyme Activation; D006801:Humans; D066298:In Vitro Techniques; D007328:Insulin / Q000494:pharmacology*; D007546:Isoquinolines / Q000494:pharmacology; D007700:Kinetics; D008970:Molecular Weight; D010766:Phosphorylation; D010879:Piperazines / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D011505:Protein-Tyrosine Kinases / Q000097:blood* / Q000302:isolation & purification; D011972:Receptor, Insulin / Q000302:isolation & purification / Q000378:metabolism*
D007328:Insulin; D007546:Isoquinolines; D010879:Piperazines; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D011505:Protein-Tyrosine Kinases; D011972:Receptor, Insulin; D011493:Protein Kinase C; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D006152:Cyclic GMP