Nerve growth factor action is mediated by cyclic AMP- and Ca+2/phospholipid-dependent protein kinases. Academic Article uri icon

Overview

abstract

  • Nerve growth factor (NGF) mediates the phosphorylation of tyrosine hydroxylase in PC12 cells on two distinct peptide fragments, separable by two-dimensional tryptic phosphopeptide mapping (phosphopeptides T1 and T3). Phorbol diester derivatives capable of activating Ca+2/phospholipid-dependent protein kinase (C-kinase) cause a specific phosphorylation of peptide T3 in a dose-dependent, saturable manner. Derivatives of the endogenous C-kinase activator diacylglycerol, also cause the phosphorylation of tyrosine hydroxylase on peptide T3. The C-kinase inhibitors chlorpromazine and trifluoperazine inhibit the phorbol diester stimulated phosphorylation of site T3 in a dose-dependent manner. These agents inhibit the phosphorylation of T3 in response to NGF, but have no effect on NGF's ability to cause T1 phosphorylation. In a PC12 mutant deficient in cAMP-dependent protein kinase activity, NGF mediates the phosphorylation of tyrosine hydroxylase on peptide T3 but not on T1. We conclude that NGF mediates the activation of both the cAMP-dependent protein kinase and the C-kinase to phosphorylate substrate proteins. These kinases can act independently to phosphorylate tyrosine hydroxylase, each at a different site, and each of which results in the enzyme activation. A molecular framework is thus provided for events underlying NGF action.

publication date

  • September 1, 1986

Research

keywords

  • Nerve Growth Factors
  • Protein Kinase C
  • Protein Kinases

Identity

PubMed Central ID

  • PMC2114293

Scopus Document Identifier

  • 0023030830

Digital Object Identifier (DOI)

  • 10.1083/jcb.103.3.887

PubMed ID

  • 2875079

Additional Document Info

volume

  • 103

issue

  • 3