TY - JOUR
T1 - Neuroprotection by neurotrophic factors and membrane depolarization is regulated by calmodulin kinase IV
AU - Pérez-García, M. José
AU - Gou-Fabregas, Myriam
AU - De Pablo, Yolanda
AU - Llovera, Marta
AU - Comella, Joan X.
AU - Soler, Rosa M.
PY - 2008/2/15
Y1 - 2008/2/15
N2 - Neurotrophic factors promote motoneuron (MN) survival through increased intracellular calcium (Ca2+) and regulation of the phosphatidylinositol (PI) 3-kinase/protein kinaseB(PKB) pathway by calmodulin (CaM). Activation of the PI 3-kinase/ PKBpathway is one of the well established mechanisms involved in MN survival. The Ca2+/CaM complex interacts with and modulates the functionality of a large number of proteins, including serine/threonine protein kinases such as Ca2+/CaM-dependent protein kinases (CaMKs). Using a primary culture of embryonic chicken spinal cord MNs, we investigated the role of CaMKIV in mediating this process. We cloned chicken CaMKIV and demonstrated its expression in purified MNs by means of reverse transcription-PCR, Western blot, and immunofluorescence. Using RNA interference, we show that endogenous CaMKIV mediates cell survival induced by neurotrophic factors or membrane depolarization. The survival effect is independent of CaMKIV kinase activity; however, CaMKIV functionality depends on the presence of Ca2+/ CaM. Finally, CaMKIV associates to the p85 subunit of PI 3-kinase in a Ca2+-dependent manner, suggesting a role in regulating PI 3-kinase/PKB activation. © 2008 by The American Society for Biochemistry and Molecular Biology, Inc.
AB - Neurotrophic factors promote motoneuron (MN) survival through increased intracellular calcium (Ca2+) and regulation of the phosphatidylinositol (PI) 3-kinase/protein kinaseB(PKB) pathway by calmodulin (CaM). Activation of the PI 3-kinase/ PKBpathway is one of the well established mechanisms involved in MN survival. The Ca2+/CaM complex interacts with and modulates the functionality of a large number of proteins, including serine/threonine protein kinases such as Ca2+/CaM-dependent protein kinases (CaMKs). Using a primary culture of embryonic chicken spinal cord MNs, we investigated the role of CaMKIV in mediating this process. We cloned chicken CaMKIV and demonstrated its expression in purified MNs by means of reverse transcription-PCR, Western blot, and immunofluorescence. Using RNA interference, we show that endogenous CaMKIV mediates cell survival induced by neurotrophic factors or membrane depolarization. The survival effect is independent of CaMKIV kinase activity; however, CaMKIV functionality depends on the presence of Ca2+/ CaM. Finally, CaMKIV associates to the p85 subunit of PI 3-kinase in a Ca2+-dependent manner, suggesting a role in regulating PI 3-kinase/PKB activation. © 2008 by The American Society for Biochemistry and Molecular Biology, Inc.
U2 - https://doi.org/10.1074/jbc.M705477200
DO - https://doi.org/10.1074/jbc.M705477200
M3 - Article
VL - 283
SP - 4133
EP - 4144
ER -