Receptor regulation of phosphoinositide 3-hydroxykinase in the NG115-401L-C3 neuronal cell line: stimulation by insulin-like growth factor-I.
The activation of phosphoinositide 3-hydroxykinase (P13K) is currently believed to represent the critical regulatory event which leads to the production of a novel intracellular signal. We have examined the control of this pathway by a number of cell-surface receptors in NG115-401L-C3 neuronal cells. Insulin-like growth factor-I stimulated the accumulation of 3-phosphorylated inositol lipids in intact cells and the appearance of P13K in antiphosphotyrosine-antibody-directed immunoprecipitates prepared from lysed cells, suggesting that P13K had been activated by a mechanism involving a protein tyrosine kinase. In contrast, P13K in these cells was not regulated by a variety of G-protein-coupled receptors, nerve growth factor acting via a low affinity receptor, or receptors for transforming growth factor-beta and interleukin-1. The receptor-specificity of P13K activation in these cells places significant constraints on the possible physiological function(s) of this pathway.
Department of Pharmaceutical Sciences, Aston University, Birmingham, U.K.
D R
DR
Poyner
M R
MR
Hanley
T R
TR
Jackson
P T
PT
Hawkins
D000818:Animals; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D004789:Enzyme Activation / Q000502:physiology; D007163:Immunosorbent Techniques; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D007700:Kinetics; D009414:Nerve Growth Factors / Q000378:metabolism; D009474:Neurons / Q000201:enzymology*; D019869:Phosphatidylinositol 3-Kinases; D018129:Phosphatidylinositol Phosphates; D010716:Phosphatidylinositols / Q000378:metabolism; D010770:Phosphotransferases / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000502:physiology*; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism
D009414:Nerve Growth Factors; D018129:Phosphatidylinositol Phosphates; D010716:Phosphatidylinositols; D011956:Receptors, Cell Surface; D017475:Receptors, Nerve Growth Factor; C060974:phosphatidylinositol 3,4,5-triphosphate; C060980:phosphatidylinositol 3,4-diphosphate; D007334:Insulin-Like Growth Factor I; D010770:Phosphotransferases; D019869:Phosphatidylinositol 3-Kinases