{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,7]],"date-time":"2026-02-07T14:27:12Z","timestamp":1770474432758,"version":"3.49.0"},"reference-count":0,"publisher":"Rockefeller University Press","issue":"3","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[1986,9,1]]},"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.1083\/jcb.103.3.887","type":"journal-article","created":{"date-parts":[[2004,5,15]],"date-time":"2004-05-15T00:18:20Z","timestamp":1084580300000},"page":"887-893","update-policy":"https:\/\/doi.org\/10.1083\/jcb.crossmarkpolicy","source":"Crossref","is-referenced-by-count":130,"title":["Nerve growth factor action is mediated by cyclic AMP- and Ca+2\/phospholipid-dependent protein kinases."],"prefix":"10.1083","volume":"103","author":[{"given":"J","family":"Cremins","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J A","family":"Wagner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S","family":"Halegoua","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"291","published-online":{"date-parts":[[1986,9,1]]},"container-title":["The Journal of cell biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/rupress.org\/jcb\/article-pdf\/103\/3\/887\/1459532\/887.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/rupress.org\/jcb\/article-pdf\/103\/3\/887\/1459532\/887.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,7,22]],"date-time":"2023-07-22T00:01:51Z","timestamp":1689984111000},"score":1,"resource":{"primary":{"URL":"https:\/\/rupress.org\/jcb\/article\/103\/3\/887\/13460\/Nerve-growth-factor-action-is-mediated-by-cyclic"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1986,9,1]]},"references-count":0,"journal-issue":{"issue":"3","published-print":{"date-parts":[[1986,9,1]]}},"URL":"https:\/\/doi.org\/10.1083\/jcb.103.3.887","relation":{},"ISSN":["0021-9525","1540-8140"],"issn-type":[{"value":"0021-9525","type":"print"},{"value":"1540-8140","type":"electronic"}],"subject":[],"published":{"date-parts":[[1986,9,1]]}}}