A bryostatin-sensitive protein kinase C required for nerve growth factor activity

Kuber R. Singh, Lori K. Taylor, Xueqiong Z. Campbell, Alan P. Fields, Alan P Fields

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Nerve growth factor (NGF) stimulates rat pheochromocytoma cells (PC12) to differentiate into a neuronal-like cell that exhibits neurite extensions. The role of protein kinase C in signal transduction has been examined in PC12 cells treated with phorbol 12-myristate 13-acetate (PMA) and bryostatin, a macrocyclic lactone that activates protein kinase C at both the nuclear and the plasma membranes [Hocevar, B. A., & Fields, A. P. (1991) J. Biol. Chem. 266, 28-33]. In contrast to PMA down-regulation [Reinhold, D. S., & Neet, K. E. (1989) J. Biol. Chem. 264, 3538-3544], chronic (24 h) treatment with bryostatin blocked the formation of neurites in response to NGF or basic fibroblast-derived growth factor stimulation, but, like PMA, bryostatin did not block the induction of c-fos or c-jun protooncogenes by NGF. Chronic bryostatin treatment down-regulated protein kinase C activity in the cytosolic, membrane, and nuclear fractions. Acute (60 min) bryostatin or NGF treatment activated cytosolic and nuclear protein kinase C activity, suggesting possible translocation to the nucleus. Bryostatin did not induce neurite outgrowth, either alone or in combination with PMA. Thus, the bryostatin-sensitive protein kinase C is distinct from PMA- or K252a-sensitive kinases previously described. The bryostatin-sensitive protein kinase C is necessary, but not sufficient, for neurite outgrowth and acts in the nucleus in a manner independent of c-fos and c-jun transcription.

Original languageEnglish (US)
Pages (from-to)542-551
Number of pages10
JournalBiochemistry
Volume33
Issue number2
StatePublished - 1994
Externally publishedYes

Fingerprint

Bryostatins
Nerve Growth Factor
Protein Kinase C
Acetates
PC12 Cells
Nuclear Envelope
Neurites
Signal transduction
Pheochromocytoma
Fibroblast Growth Factor 2
Lactones
Transcription
Fibroblasts
Cell membranes
Nuclear Proteins
Rats
Signal Transduction
Intercellular Signaling Peptides and Proteins
Phosphotransferases
Down-Regulation

ASJC Scopus subject areas

  • Biochemistry

Cite this

Singh, K. R., Taylor, L. K., Campbell, X. Z., Fields, A. P., & Fields, A. P. (1994). A bryostatin-sensitive protein kinase C required for nerve growth factor activity. Biochemistry, 33(2), 542-551.

A bryostatin-sensitive protein kinase C required for nerve growth factor activity. / Singh, Kuber R.; Taylor, Lori K.; Campbell, Xueqiong Z.; Fields, Alan P.; Fields, Alan P.

In: Biochemistry, Vol. 33, No. 2, 1994, p. 542-551.

Research output: Contribution to journalArticle

Singh, KR, Taylor, LK, Campbell, XZ, Fields, AP & Fields, AP 1994, 'A bryostatin-sensitive protein kinase C required for nerve growth factor activity', Biochemistry, vol. 33, no. 2, pp. 542-551.
Singh, Kuber R. ; Taylor, Lori K. ; Campbell, Xueqiong Z. ; Fields, Alan P. ; Fields, Alan P. / A bryostatin-sensitive protein kinase C required for nerve growth factor activity. In: Biochemistry. 1994 ; Vol. 33, No. 2. pp. 542-551.
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