Inositol 1,4,5-trisphosphate stimulates phosphorylation of a 62,000-dalton protein in monkey fibroblast and bovine brain cell lysates.
Inositol 1,4,5-trisphosphate (IP3) is produced in cells as a breakdown product of the diphosphorylated form of phosphatidylinositol, phosphatidylinositol 4,5-bisphosphate. Stimulated breakdown of phosphoinositides has been correlated with a wide variety of hormonal stimuli which mobilize intracellular calcium, and IP3 has recently been found to cause calcium release from intracellular stores, thus implicating it as a second messenger in hormonal stimulation. In this paper we have examined the effect of IP3 on protein phosphorylation, and have found that IP3 stimulates phosphorylation of a 62-kDa protein in cell lysates made from cultured monkey fibroblasts and from bovine brain. Fifty per cent maximal stimulation of phosphorylation of this protein occurred at 2.5 X 10(-7) M IP3. Other inositol phosphates (inositol 1,4-bisphosphate, inositol 1-phosphate, inositol hexaphosphate, and myo-inositol) had no effect on protein phosphorylation at 10(-6)M, although inositol 1,4-bisphosphate at higher concentrations enhanced phosphorylation of the 62-kDa protein in brain lysates. The IP3-stimulated phosphorylation was calcium-independent and did not appear to result from inhibition of an endogenous protein phosphatase. We suggest that IP3, like other second messengers, acts as a protein kinase regulator.
D000818:Animals; D001921:Brain / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism*; D000882:Haplorhini; D015544:Inositol 1,4,5-Trisphosphate; D007295:Inositol Phosphates / Q000494:pharmacology*; D008970:Molecular Weight; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism*; D013403:Sugar Phosphates / Q000494:pharmacology*
D007295:Inositol Phosphates; D011506:Proteins; D013403:Sugar Phosphates; D015544:Inositol 1,4,5-Trisphosphate; D011494:Protein Kinases; D002118:Calcium