PMID- 11489918
OWN - NLM
STAT- MEDLINE
DCOM- 20010906
LR  - 20211203
IS  - 0021-9525 (Print)
IS  - 1540-8140 (Electronic)
IS  - 0021-9525 (Linking)
VI  - 154
IP  - 3
DP  - 2001 Aug 6
TI  - Neuronal survival induced by neurotrophins requires calmodulin.
PG  - 585-97
AB  - It has been reported that phosphoinositide 3-kinase (PI 3-kinase) and its 
      downstream target, protein kinase B (PKB), play a central role in the signaling 
      of cell survival triggered by neurotrophins (NTs). In this report, we have 
      analyzed the involvement of Ca2+ and calmodulin (CaM) in the activation of the 
      PKB induced by NTs. We have found that reduction of intracellular Ca2+ 
      concentration or functional blockade of CaM abolished NGF-induced activation of 
      PKB in PC12 cells. Similar results were obtained in cultures of chicken spinal 
      cord motoneurons treated with brain-derived neurotrophic factor (BDNF). Moreover, 
      CaM inhibition prevented the cell survival triggered by NGF or BDNF. This effect 
      was counteracted by the transient expression of constitutive active forms of the 
      PKB, indicating that CaM regulates NT-induced cell survival through the 
      activation of the PKB. We have investigated the mechanisms whereby CaM regulates 
      the activation of the PKB, and we have found that CaM was necessary for the 
      proper generation and/or accumulation of the products of the PI 3-kinase in 
      intact cells.
FAU - Egea, J
AU  - Egea J
AD  - Grup de Neurobiologia Molecular, Departament de Ciencies Mediques Basiques, 
      Facultat de Medicina, Universitat de Lleida, 25198 Lleida, Catalonia, Spain.
FAU - Espinet, C
AU  - Espinet C
FAU - Soler, R M
AU  - Soler RM
FAU - Dolcet, X
AU  - Dolcet X
FAU - Yuste, V J
AU  - Yuste VJ
FAU - Encinas, M
AU  - Encinas M
FAU - Iglesias, M
AU  - Iglesias M
FAU - Rocamora, N
AU  - Rocamora N
FAU - Comella, J X
AU  - Comella JX
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Cell Biol
JT  - The Journal of cell biology
JID - 0375356
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Calmodulin)
RN  - 0 (Chelating Agents)
RN  - 0 (Chromones)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Indicators and Reagents)
RN  - 0 (Luminescent Proteins)
RN  - 0 (Morpholines)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Sulfonamides)
RN  - 147336-22-9 (Green Fluorescent Proteins)
RN  - 31M2U1DVID (2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one)
RN  - 526U7A2651 (Egtazic Acid)
RN  - 81705-04-6 (N-(4-aminobutyl)-5-chloro-2-naphthalenesulfonamide)
RN  - 9061-61-4 (Nerve Growth Factor)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinases)
RN  - K22DDW77C0 (1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/*pharmacology
MH  - Calcium/metabolism
MH  - Calcium-Calmodulin-Dependent Protein Kinases/metabolism
MH  - Calmodulin/antagonists & inhibitors/*metabolism
MH  - Cell Membrane/metabolism
MH  - Cell Survival/drug effects/physiology
MH  - Chelating Agents/pharmacology
MH  - Chromones/pharmacology
MH  - Egtazic Acid/analogs & derivatives/pharmacology
MH  - Enzyme Inhibitors/pharmacology
MH  - Green Fluorescent Proteins
MH  - Indicators and Reagents/metabolism
MH  - Luminescent Proteins/genetics
MH  - Morpholines/pharmacology
MH  - Nerve Growth Factor/*pharmacology
MH  - Neurons/*cytology/*enzymology
MH  - PC12 Cells
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Phosphorylation
MH  - *Protein Serine-Threonine Kinases
MH  - Proto-Oncogene Proteins/genetics/metabolism
MH  - Proto-Oncogene Proteins c-akt
MH  - Rats
MH  - Recombinant Proteins/metabolism
MH  - Signal Transduction/physiology
MH  - Sulfonamides/pharmacology
PMC - PMC2196427
EDAT- 2001/08/08 10:00
MHDA- 2001/09/08 10:01
PMCR- 2002/02/06
CRDT- 2001/08/08 10:00
PHST- 2001/08/08 10:00 [pubmed]
PHST- 2001/09/08 10:01 [medline]
PHST- 2001/08/08 10:00 [entrez]
PHST- 2002/02/06 00:00 [pmc-release]
AID - 154/3/585 [pii]
AID - 0101023 [pii]
AID - 10.1083/jcb.200101023 [doi]
PST - ppublish
SO  - J Cell Biol. 2001 Aug 6;154(3):585-97. doi: 10.1083/jcb.200101023.