NCAM signaling for neurite out-growth

Stable Identifier
R-HSA-375165
Type
Pathway
Species
Homo sapiens
Compartment
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Summation

The neural cell adhesion molecule, NCAM, is a member of the immunoglobulin (Ig) superfamily and is involved in a variety of cellular processes of importance for the formation and maintenance of the nervous system. The role of NCAM in neural differentiation and synaptic plasticity is presumed to depend on the modulation of intracellular signal transduction cascades. NCAM based signaling complexes can initiate downstream intracellular signals by at least two mechanisms: (1) activation of FGFR and (2) formation of intracellular signaling complexes by direct interaction with cytoplasmic interaction partners such as Fyn and FAK. Tyrosine kinases Fyn and FAK interact with NCAM and undergo phosphorylation and this transiently activates the MAPK, ERK 1 and 2, cAMP response element binding protein (CREB) and transcription factors ELK and NFkB. CREB activates transcription of genes which are important for axonal growth, survival, and synaptic plasticity in neurons.

NCAM1 mediated intracellular signal transduction is represented in the figure below. The Ig domains in NCAM1 are represented in orange ovals and Fn domains in green squares. The tyrosine residues susceptible to phosphorylation are represented in red circles and their positions are numbered. Phosphorylation is represented by red arrows and dephosphorylation by yellow. Ig, Immunoglobulin domain; Fn, Fibronectin domain; Fyn, Proto-oncogene tyrosine-protein kinase Fyn; FAK, focal adhesion kinase; RPTPalpha, Receptor-type tyrosine-protein phosphatase; Grb2, Growth factor receptor-bound protein 2; SOS, Son of sevenless homolog; Raf, RAF proto-oncogene serine/threonine-protein kinase; MEK, MAPK and ERK kinase; ERK, Extracellular signal-regulated kinase; MSK1, Mitogen and stress activated protein kinase 1; CREB, Cyclic AMP-responsive element-binding protein; CRE, cAMP response elements.

Literature References
PubMed ID Title Journal Year
12587671 Intracellular signaling by the neural cell adhesion molecule

Povlsen, GK, Ditlevsen, DK, Berezin, V, Bock, E

Neurochem Res 2003
15153429 Regulators of neurite outgrowth: role of cell adhesion molecules

Kiryushko, D, Berezin, V, Bock, E

Ann N Y Acad Sci 2004
17975827 NCAM-induced intracellular signaling revisited

Ditlevsen, DK, Povlsen, GK, Berezin, V, Bock, E

J Neurosci Res 2008
15662836 Zippers make signals: NCAM-mediated molecular interactions and signal transduction

Walmod, PS, Kolkova, K, Berezin, V, Bock, E

Neurochem Res 2004
12700044 Cellular signalling mechanisms of neural cell adhesion molecules

Panicker, AK, Buhusi, M, Thelen, K, Maness, PF

Front Biosci 2003
18760361 L1 and NCAM adhesion molecules as signaling coreceptors in neuronal migration and process outgrowth

Schmid, RS, Maness, PF

Curr Opin Neurobiol 2008
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