The GPI-anchored adhesion molecule F3 induces tyrosine phosphorylation: involvement of the FNIII repeats.
The glycosyl-phosphatidylinositol (GPI)-anchored F3 molecule, a member of the Ig superfamily made up of Ig and FNIII-like domains, is involved in cell-cell adhesion, neuronal pathfinding and fasciculation. Little is known about the mechanism(s) that governs the F3-mediated cell-cell recognition. In particular, it is not known whether F3 transduces signals across the membrane. Here we show that in F3-transfected CHO cells (1A cells) an increase in tyrosine phosphorylation occurs during F3-mediated aggregation. Moreover, under aggregation conditions F3 immunoprecipitated from 32P-metabolically labeled 1A cells associated with three major phosphorylated proteins. Interestingly, genistein inhibited the F3-mediated aggregation. Increased tyrosine phosphorylation was also observed using antibody-mediated F3-cross-linking. Furthermore, F3 expressed both in 1A cells and in post-natal mouse cerebellum forms non-covalent soluble complexes with protein tyrosine kinase(s). In cerebellum the F3-associated kinase was identified as fyn. By contrast, a truncated F3 protein, expressed in CHO cells, from which all the FN type III repeats have been deleted, does not associate with a kinase. Cross-linking of the F3-truncated form does not induce modulation of tyrosine phosphorylation. Taken together these data demonstrate that F3 is a molecule that transduces signals through both association with protein tyrosine kinase and modulation of protein tyrosine phosphorylation. The presence of FN type III domains is essential for the activation of the intracellular signaling pathway.
Laboratoire de Genetique et de Physiologie du Developpement, Faculte des sciences de Luminy, Marseille, France.
M
M
Cervello
V
V
Matranga
P
P
Durbec
G
G
Rougon
S
S
Gomez
D000818:Animals; D016466:CHO Cells; D015816:Cell Adhesion Molecules, Neuronal / Q000494:pharmacology*; D058966:Contactins; D006224:Cricetinae; D005353:Fibronectins / Q000737:chemistry*; D017261:Glycosylphosphatidylinositols; D010766:Phosphorylation; D017434:Protein Structure, Tertiary; D012091:Repetitive Sequences, Nucleic Acid; D014443:Tyrosine / Q000737:chemistry*
D015816:Cell Adhesion Molecules, Neuronal; D058966:Contactins; D005353:Fibronectins; D017261:Glycosylphosphatidylinositols; D014443:Tyrosine