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Activation of the MAPK Signal Cascade by the Neural Cell Adhesion Molecule L1 Requires L1 Internalization
Ist Teil von
The Journal of biological chemistry, 1999-12, Vol.274 (53), p.37965-37973
Ort / Verlag
United States: American Society for Biochemistry and Molecular Biology
Erscheinungsjahr
1999
Quelle
MEDLINE
Beschreibungen/Notizen
L1-mediated axon growth involves intracellular signaling, but the precise mechanisms involved are not yet clear. We report
a role for the mitogen-activated protein kinase (MAPK) cascade in L1 signaling. L1 physically associates with the MAPK cascade
components Raf-1, ERK2, and the previously identified p90 rsk in brain. In vitro , ERK2 can phosphorylate L1 at Ser 1204 and Ser 1248 of the L1 cytoplasmic domain. These two serines are conserved in the L1 family of cell adhesion molecules, also being found
in neurofascin and NrCAM. The ability of ERK2 to phosphorylate L1 suggests that L1 signaling could directly regulate L1 function
by phosphorylation of the L1 cytoplasmic domain. In L1-expressing 3T3 cells, L1 cross-linking can activate ERK2. Remarkably,
the activated ERK localizes with endocytosed vesicular L1 rather than cell surface L1, indicating that L1 internalization
and signaling are coupled. Inhibition of L1 internalization with dominant-negative dynamin prevents activation of ERK. These
results show that L1-generated signals activate the MAPK cascade in a manner most likely to be important in regulating L1
intracellular trafficking.