QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (25) Citing Articles via Google Scholar Google Scholar Articles by Massé, T. Articles by Kelly, P. T. Search for Related Content PubMed PubMed Citation Articles by Massé, T. Articles by Kelly, P. T.

 Previous Article  |  Next Article 

Volume 17, Number 3, Issue of February 1, 1997 pp. 924-931
Copyright ©1997 Society for Neuroscience

Overexpression of Ca²⁺/Calmodulin-Dependent Protein Kinase II in PC12 Cells Alters Cell Growth, Morphology, and Nerve Growth Factor-Induced Differentiation

Received May 2, 1996; revised Oct. 31, 1996; accepted Nov. 11, 1996.

Thierry Massé¹ and Paul T. Kelly²

¹ Immuno-Virologie Moleculaire et Cellulaire, Centre National de la Recherche Scientifique-UMR 5537, Faculte de Medecine Lyon-Laënnec, 69372 Lyon Cedex 08, France, and ² Department of Neurobiology and Anatomy, University of Texas Medical School, Houston, Texas 77225

To examine the role of Ca²⁺/calmodulin-dependent protein kinase II (CaMKII) in cell differentiation and neuronal functions, stable transformants of PC12 cells were established that expressed levels of the -subunit of CaMKII (CaMKII) equivalent to mammalian neurons. The expression of the transfected CaMKII gene or the endogenous CaMKII gene was monitored by RNase protection assays, and CaMKII protein expression was determined by Western blots. Several PC12-derived clones expressed amounts of CaMKII mRNA and CaMKII protein similar to that of hippocampal tissues and several orders of magnitude greater than untransfected PC12 cells. CaMKII catalytic activity was four times higher in extracts from CaMKII-overexpressing compared with untransfected PC12 cells. All clones overexpressing CaMKII displayed altered cellular growth and adhesion properties including increased cell-to-substrate adhesion, decreased cell-to-cell adhesion, enhanced contact inhibition, and prolonged survival at confluency. Furthermore, the CaMKII activity in overexpressing PC12 cells inhibited neurite elongation during NGF-induced differentiation. Inhibition of CaMKII activity in vivo with KN-62 caused the morphological phenotypes of CaMKII-overexpressing cells to partially revert to that of untransfected PC12 cells. These results show that CaMKII catalytic activity affects growth, morphology, and NGF-induced differentiation of PC12 cells.

Key words: cell Ca²⁺; cytoskeleton; growth cone; neurite; nerve growth factor; PC12 cells; Ca²⁺/calmodulin-dependent protein kinase

This article has been cited by other articles:

				Y. Jing, J. A. Dowdy, M. R. Van Scott, and J. S. Fedan Hyperosmolarity-Induced Dilation and Epithelial Bioelectric Responses of Guinea Pig Trachea in Vitro: Role of Kinase Signaling J. Pharmacol. Exp. Ther., July 1, 2008; 326(1): 186 - 195. [Abstract] [Full Text] [PDF]

				L. W. Kutcher, S. R. Beauman, E. I. Gruenstein, M. A. Kaetzel, and J. R. Dedman Nuclear CaMKII inhibits neuronal differentiation of PC12 cells without affecting MAPK or CREB activation Am J Physiol Cell Physiol, June 1, 2003; 284(6): C1334 - C1345. [Abstract] [Full Text] [PDF]

				A. Ohyama, K. Hosaka, Y. Komiya, K. Akagawa, E. Yamauchi, H. Taniguchi, N. Sasagawa, K. Kumakura, S. Mochida, T. Yamauchi, et al. Regulation of Exocytosis through Ca2+/ATP-Dependent Binding of Autophosphorylated Ca2+/Calmodulin-Activated Protein Kinase II to Syntaxin 1A J. Neurosci., May 1, 2002; 22(9): 3342 - 3351. [Abstract] [Full Text] [PDF]

				N. Caran, L. D. Johnson, K. J. Jenkins, and R. M. Tombes Cytosolic Targeting Domains of gamma and delta Calmodulin-dependent Protein Kinase II J. Biol. Chem., November 2, 2001; 276(45): 42514 - 42519. [Abstract] [Full Text] [PDF]

				M. R. Hansen, X.-M. Zha, J. Bok, and S. H. Green Multiple Distinct Signal Pathways, Including an Autocrine Neurotrophic Mechanism, Contribute to the Survival-Promoting Effect of Depolarization on Spiral Ganglion Neurons In Vitro J. Neurosci., April 1, 2001; 21(7): 2256 - 2267. [Abstract] [Full Text] [PDF]

				T. Olli-Lahdesmaki, J. Kallio, and M. Scheinin Receptor Subtype-Induced Targeting and Subtype-Specific Internalization of Human alpha 2-Adrenoceptors in PC12 Cells J. Neurosci., November 1, 1999; 19(21): 9281 - 9288. [Abstract] [Full Text] [PDF]

				B. Hoch, R. Meyer, R. Hetzer, E.-G. Krause, and P. Karczewski Identification and Expression of {delta}-Isoforms of the Multifunctional Ca2+/Calmodulin-Dependent Protein Kinase in Failing and Nonfailing Human Myocardium Circ. Res., April 2, 1999; 84(6): 713 - 721. [Abstract] [Full Text] [PDF]

				G. Wu and H. T. Cline Stabilization of Dendritic Arbor Structure in Vivo by CaMKII Science, January 9, 1998; 279(5348): 222 - 226. [Abstract] [Full Text]

				T. B. Kuhn, C. V. Williams, P. Dou, and S. B. Kater Laminin Directs Growth Cone Navigation via Two Temporally and Functionally Distinct Calcium Signals J. Neurosci., January 1, 1998; 18(1): 184 - 194. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help