PT  - JOURNAL ARTICLE
AU  - Massé, Thierry
AU  - Kelly, Paul T.
TI  - Overexpression of Ca<sup>2+</sup>/Calmodulin-Dependent Protein Kinase II in PC12 Cells Alters Cell Growth, Morphology, and Nerve Growth Factor-Induced Differentiation
AID  - 10.1523/JNEUROSCI.17-03-00924.1997
DP  - 1997 Feb 01
TA  - The Journal of Neuroscience
PG  - 924--931
VI  - 17
IP  - 3
4099  - http://www.jneurosci.org/content/17/3/924.short
4100  - http://www.jneurosci.org/content/17/3/924.full
SO  - J. Neurosci.1997 Feb 01; 17
AB  - 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 α-subunit of CaMKII (αCaMKII) equivalent to mammalian neurons. The expression of the transfected αCaMKII gene or the endogenous βCaMKII gene was monitored by RNase protection assays, and αCaMKII protein expression was determined by Western blots. Several PC12-derived clones expressed amounts of αCaMKII mRNA and αCaMKII 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 αCaMKII-overexpressing compared with untransfected PC12 cells. All clones overexpressing αCaMKII 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 αCaMKII 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 αCaMKII-overexpressing cells to partially revert to that of untransfected PC12 cells. These results show that αCaMKII catalytic activity affects growth, morphology, and NGF-induced differentiation of PC12 cells.