TY - JOUR
T1 - The transcription factors CREB and c-Fos play key roles in NCAM-mediated neuritogenesis in PC12-E2 cells
AU - Jessen, U
AU - Novitskaya, V
AU - Pedersen, N
AU - Serup, P
AU - Berezin, V
AU - Bock, E
N1 - Keywords: Animals; Arachidonic Acid; Axons; Bucladesine; Carbazoles; Cells, Cultured; Cyclic AMP; Cyclic AMP Response Element-Binding Protein; Cyclic AMP-Dependent Protein Kinases; Enzyme Inhibitors; Genes, Reporter; Genes, fos; Hippocampus; Indoles; MAP Kinase Kinase 2; MAP Kinase Signaling System; Mitogen-Activated Protein Kinase Kinases; Models, Biological; Neoplasm Proteins; Nerve Tissue Proteins; Neural Cell Adhesion Molecules; Neurites; PC12 Cells; Phosphorylation; Protein Processing, Post-Translational; Protein-Tyrosine Kinases; Proto-Oncogene Proteins c-fos; Pyrroles; Rats; Recombinant Fusion Proteins; Reverse Transcriptase Polymerase Chain Reaction; Signal Transduction; Thionucleotides; Transcription, Genetic; Transfection
PY - 2001
Y1 - 2001
N2 - The neural cell adhesion molecule (NCAM) stimulates axonal outgrowth by activation of the Ras-mitogen activated protein kinase (MAPK) pathway and by generation of arachidonic acid. We investigated whether the transcription factors, cyclic-AMP response-element binding protein (CREB) and c-Fos play roles in this process by estimating NCAM-dependent neurite outgrowth from PC12-E2 cells grown in co-culture with NCAM-negative or NCAM-positive fibroblasts. PC12-E2 cells were transiently transfected with expression plasmids encoding wild-type or dominant negative forms of CREB and c-Fos or an activated form of the MAPK kinase, MEK2. Alternatively, PC12-E2 cells were treated with arachidonic acid, the cAMP analogue dBcAMP, or protein kinase A (PKA) inhibitors. The negative forms of CREB and c-Fos inhibited neurite outgrowth mediated by NCAM, arachidonic acid, dBcAMP, or MEK2. Neither CREB nor c-Fos could compensate for the inactivation of the other, indicating that both factors are important in NCAM-mediated neuritogenesis. Treatment of primary hippocampal neurons with a synthetic NCAM peptide ligand known to stimulate neurite outgrowth induced phosphorylation of CREB and expression of c-fos. We thus present evidence that NCAM-mediated neurite outgrowth involves a series of signal transduction pathways, including the cAMP/PKA pathway, targeting c-Fos and CREB.
AB - The neural cell adhesion molecule (NCAM) stimulates axonal outgrowth by activation of the Ras-mitogen activated protein kinase (MAPK) pathway and by generation of arachidonic acid. We investigated whether the transcription factors, cyclic-AMP response-element binding protein (CREB) and c-Fos play roles in this process by estimating NCAM-dependent neurite outgrowth from PC12-E2 cells grown in co-culture with NCAM-negative or NCAM-positive fibroblasts. PC12-E2 cells were transiently transfected with expression plasmids encoding wild-type or dominant negative forms of CREB and c-Fos or an activated form of the MAPK kinase, MEK2. Alternatively, PC12-E2 cells were treated with arachidonic acid, the cAMP analogue dBcAMP, or protein kinase A (PKA) inhibitors. The negative forms of CREB and c-Fos inhibited neurite outgrowth mediated by NCAM, arachidonic acid, dBcAMP, or MEK2. Neither CREB nor c-Fos could compensate for the inactivation of the other, indicating that both factors are important in NCAM-mediated neuritogenesis. Treatment of primary hippocampal neurons with a synthetic NCAM peptide ligand known to stimulate neurite outgrowth induced phosphorylation of CREB and expression of c-fos. We thus present evidence that NCAM-mediated neurite outgrowth involves a series of signal transduction pathways, including the cAMP/PKA pathway, targeting c-Fos and CREB.
M3 - Journal article
C2 - 11752056
SN - 0022-3042
VL - 79
SP - 1149
EP - 1160
JO - Journal of Neurochemistry
JF - Journal of Neurochemistry
IS - 6
ER -