Nerve Growth Factor‐Induced Down‐Regulation of Calmodulin‐Dependent Protein Kinase III in PC12 Cells Involves Cyclic AMP‐Dependent Protein Kinase
- 1 March 1990
- journal article
- research article
- Published by Wiley in Journal of Neurochemistry
- Vol. 54 (3), 1034-1039
- https://doi.org/10.1111/j.1471-4159.1990.tb02354.x
Abstract
Treatment of PC12 cells with nerve growth factor (NGF), epidermal growth factor (EGF), or agents that raise intracellular cyclic AMP (cAMP) levels (e.g., forskolin) reduces the activity of calmodulin-dependent protein kinase III (CaM-PK III) over a period of 8 h. The mechanism of this effect of NGF has now been examined in more detail, making use of a mutant PC12 cell line (A126-1B2) that is deficient in cAMP-dependent protein kinase activity. Control experiments showed that A126-1B2 cells retain other NGF-mediated responses (e.g., the induction o fornithine decarboxylase, a cAMP-independent event) and contain a complement of CaM-PK III and its substrate, elongation factor-2, comparable to that of wild-tpe cells. The ability of NGF or forskolin, but not of EGF, to down-regulate CaM-PK III was markedly attenuated in a126-1B2 compared to wild-type cells. Treatment of wild-type cells with the cAMP phosphodiesterase inhibitor, isobutylmethylxanthine, enhanced the effects of NGF, bu tnot to EGF. The possibility that NGF led to a stimulation of cAMP-dependent protein kinase activity in wild-type cells was assessed by measurement of the "activation ratio" (-cAMP/+cAMP) of this enzyme before and at various times after NGF addition. A small, but significant, increasein the activation ratio from 0.3 to 0.48 was observed, reaching a peak 5 min after NGF treatment. EGF had no effect on the activation ratio in wild-type cells. These experiments support the hypothesis that NGF, but not EGF, achieves its effects on CaM-PK III by activation of a cAMP-dependent protein kinase and suggest that other actions of NGF may be mediated by the same mechanism.Keywords
This publication has 50 references indexed in Scilit:
- Calmodulin‐ and protein phosphorylation‐independent release of catecholamines from PC‐12 cellsFEBS Letters, 1988
- Early rise of cytosolic Ca2+ induced by NGF in PC12 and chromaffin cellsFEBS Letters, 1986
- Nerve growth factor action is mediated by cyclic AMP- and Ca+2/phospholipid-dependent protein kinases.The Journal of cell biology, 1986
- The role of cAMP in nerve growth factor-promoted neurite outgrowth in PC12 cells.The Journal of cell biology, 1986
- Nerve growth factor- and epidermal growth factor-stimulated phosphorylation of a PC12 cytoskeletally associated protein in situ.The Journal of cell biology, 1985
- Nerve growth factor mediates phosphorylation of specific proteinsCell, 1980
- Ca2+ transmembrane fluxes and nerve growth factor action on a clonal cell line of rat phaeochromocytomaNature, 1980
- Induction of ornithine decarboxylase by nerve growth factor dissociated from effects on survival and neurite outgrowthNature, 1978
- Nerve growth factor‐mediated selective induction of ornithine decarboxylase in rat pheochromocytoma; a cyclic amp‐independent processFEBS Letters, 1978
- Alterations in the surface properties of cells responsive to nerve growth factorNature, 1978