PMID- 10084688
OWN - NLM
STAT- MEDLINE
DCOM- 19990511
LR  - 20191210
IS  - 0022-3034 (Print)
IS  - 0022-3034 (Linking)
VI  - 38
IP  - 4
DP  - 1999 Mar
TI  - NCAM stimulates the Ras-MAPK pathway and CREB phosphorylation in neuronal cells.
PG  - 542-58
AB  - The neural cell adhesion molecule NCAM plays an important role in axonal growth, 
      learning, and memory. A signaling pathway has been elucidated in which clustering
      of the NCAM140 isoform in the neural plasma membrane stimulated the activating
      phosphorylation of mitogen-activated protein kinases (MAPKs) and the
      transcription factor cyclic AMP response-element binding protein (CREB). NCAM
      clustering transiently induced dual phosphorylation (activation) of the MAPKs
      ERK1 and ERK2 (extracellular signal-regulated kinases) by a pathway regulated by 
      the focal adhesion kinase p125fak, p59fyn, Ras, and MAPK kinase. CREB
      phosphorylation at serine 133 induced by NCAM was dependent in part on an intact 
      MAPK pathway. c-Jun N-terminal kinase, which is associated with apoptosis and
      cellular stress, was not activated by NCAM. Inhibition of the MAPK pathway in rat
      cerebellar neuron cultures selectively reduced NCAM-stimulated neurite outgrowth.
      These results define an NCAM signal transduction mechanism with the potential for
      modulating the expression of genes needed for axonal growth, survival, and
      synaptic plasticity.
FAU - Schmid, R S
AU  - Schmid RS
AD  - Department of Biochemistry, School of Medicine, University of North Carolina,
      Chapel Hill 27599-7260, USA.
FAU - Graff, R D
AU  - Graff RD
FAU - Schaller, M D
AU  - Schaller MD
FAU - Chen, S
AU  - Chen S
FAU - Schachner, M
AU  - Schachner M
FAU - Hemperly, J J
AU  - Hemperly JJ
FAU - Maness, P F
AU  - Maness PF
LA  - eng
GR  - HD35170/HD/NICHD NIH HHS/United States
GR  - NS26620/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Neurobiol
JT  - Journal of neurobiology
JID - 0213640
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Cyclic AMP Response Element-Binding Protein)
RN  - 0 (Neural Cell Adhesion Molecules)
RN  - 0 (Recombinant Fusion Proteins)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinases)
RN  - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - EC 3.6.5.2 (ras Proteins)
SB  - IM
MH  - Animals
MH  - Antibodies, Monoclonal/pharmacology
MH  - Calcium-Calmodulin-Dependent Protein Kinases/*metabolism
MH  - Cyclic AMP Response Element-Binding Protein/*metabolism
MH  - JNK Mitogen-Activated Protein Kinases
MH  - L Cells
MH  - Mice
MH  - Mitogen-Activated Protein Kinase 1
MH  - Mitogen-Activated Protein Kinase 3
MH  - *Mitogen-Activated Protein Kinases
MH  - Neural Cell Adhesion Molecules/genetics/immunology/*physiology
MH  - Neurites/*physiology
MH  - Neuroblastoma
MH  - Neurons/*metabolism
MH  - Phosphorylation
MH  - Rats
MH  - Recombinant Fusion Proteins/metabolism
MH  - Signal Transduction
MH  - Transfection
MH  - Tumor Cells, Cultured
MH  - ras Proteins/*metabolism
EDAT- 1999/03/20 03:13
MHDA- 2000/06/20 09:00
CRDT- 1999/03/20 03:13
PHST- 1999/03/20 03:13 [pubmed]
PHST- 2000/06/20 09:00 [medline]
PHST- 1999/03/20 03:13 [entrez]
AID - 10.1002/(SICI)1097-4695(199903)38:4<542::AID-NEU9>3.0.CO;2-1 [pii]
PST - ppublish
SO  - J Neurobiol. 1999 Mar;38(4):542-58.