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The role of phosphatidylinositol 3‐kinase in neural cell adhesion molecule‐mediated neuronal differentiation and survival
Author(s) -
Ditlevsen Dorte K.,
Køhler Lene B.,
Pedersen Martin V.,
Risell Michael,
Kolkova Kateryna,
Meyer Morten,
Berezin Vladimir,
Bock Elisabeth
Publication year - 2003
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.1471-4159.2003.01538.x
Subject(s) - neural cell adhesion molecule , neurite , microbiology and biotechnology , protein kinase b , protein kinase a , biology , pi3k/akt/mtor pathway , phosphatidylinositol , chemistry , kinase , signal transduction , cell adhesion , biochemistry , cell , in vitro
The neural cell adhesion molecule, NCAM, is known to stimulate neurite outgrowth from primary neurones and PC12 cells presumably through signalling pathways involving the fibroblast growth factor receptor (FGFR), protein kinase A (PKA), protein kinase C (PKC), the Ras‐mitogen activated protein kinase (MAPK) pathway and an increase in intracellular Ca 2+ levels. Stimulation of neurones with the synthetic NCAM‐ligand, C3, induces neurite outgrowth through signalling pathways similar to the pathways activated through physiological, homophilic NCAM‐stimulation. We present here data indicating that phosphatidylinositol 3‐kinase (PI3K) is required for NCAM‐mediated neurite outgrowth from PC12‐E2 cells and from cerebellar and dopaminergic neurones in primary culture, and that the thr/ser kinase Akt/protein kinase B (PKB) is phosphorylated downstream of PI3K after stimulation with C3. Moreover, we present data indicating a survival‐promoting effect of NCAM‐stimulation by C3 on cerebellar and dopaminergic neurones induced to undergo apoptosis. This protective effect of C3 included an inhibition of both DNA‐fragmentation and caspase‐3 activation. The survival‐promoting effect of NCAM‐stimulation was also shown to be dependent on PI3K.