Tyrosine 734 of NCAM180 interferes with FGF receptor-dependent signaling implicated in neurite growth.
The cytoplasmic domain of the neural cell adhesion molecule (NCAM) contains multiple phosphorylation sites. We report here that in addition to serine and threonine residues a tyrosine of the NCAM180 isoform is phosphorylated as shown by phosphoamino acid analysis. Exchange of the only cytoplasmic tyrosine at position 734 of human NCAM180 (NCAM180-Y734F) to phenylalanine resulted in increased neurite outgrowth of NCAM180-Y734F transfected B35 neuroblastoma cells compared to NCAM180-wt transfectants on poly-L-lysine as substrate. As demonstrated by inhibitor studies the increased neurite outgrowth was due to higher FGF receptor 1 and ERK1 activity in NCAM180-Y734F cells, indicating that tyrosine residue 734 plays a role in signal transduction mediated by the FGF receptor. On an NCAM expressing monolayer of COS-7 cells the Y734F mutation also influences FGF receptor 1 dependent neurite outgrowth, but under these conditions additional mechanisms seem to be responsible for the increased neurite length observed for NCAM180-Y734F transfected cells.
Department of Biochemistry, Institute of Physiology, Biochemistry and Animal Health, Katzenburgweg 9a, 53115 Bonn, Germany.
Simone
S
Diestel
Christine
C
Laurini
Otto
O
Traub
Brigitte
B
Schmitz
D000818:Animals; D001932:Brain Neoplasms / Q000378:metabolism / Q000473:pathology; D019556:COS Cells; D002455:Cell Division; D002460:Cell Line; D002522:Chlorocebus aethiops; D006801:Humans; D019006:Neural Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D016501:Neurites / Q000378:metabolism* / Q000473:pathology*; D009447:Neuroblastoma / Q000378:metabolism* / Q000473:pathology*; D051381:Rats; D017468:Receptors, Fibroblast Growth Factor / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D015398:Signal Transduction; D013329:Structure-Activity Relationship; D014443:Tyrosine / Q000235:genetics / Q000378:metabolism*
D019006:Neural Cell Adhesion Molecules; D017468:Receptors, Fibroblast Growth Factor; D011994:Recombinant Proteins; D014443:Tyrosine