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The transcription factors CREB and c‐Fos play key roles in NCAM‐mediated neuritogenesis in PC12‐E2 cells
Author(s) -
Jessen Ulla,
Novitskaya Vera,
Pedersen Nina,
Serup Palle,
Berezin Vladimir,
Bock Elisabeth
Publication year - 2001
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2001.00636.x
Subject(s) - creb , neurite , neural cell adhesion molecule , microbiology and biotechnology , cyclic amp response element binding protein , protein kinase a , signal transduction , mapk/erk pathway , transcription factor , biology , chemistry , kinase , biochemistry , cell adhesion , in vitro , cell , gene
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.