Signaling events following the interaction of the neuronal adhesion molecule F3 with the N-terminal domain of tenascin-R.
Interaction between the extracellular matrix protein tenascin-R and the neuronal adhesion molecule F3 might be involved in the formation of neuronal networks. In this study, the fragment of tenascin-R comprising epithelial growth factor (EGF)-like repeats and the cysteine-rich NH2 terminal stretch (EGF-L), known to be inhibitory for growing neurites and repellent for growth cones, was used to investigate the signaling events following the F3/EGF-L interaction. We addressed this question using an in vitro test with F3-transfected Chinese hamster ovary (CHO) cells that allowed us to measure the kinetics, magnitude and specificity of the repellent effect resulting from the specific F3/EGF-L interaction. We showed that the repellent effect was counteracted by addition of the serine/threonine kinase and -phosphatase modulators (staurosporine, okadaic acid and H7) but not by modulators of tyrosine kinase or -phosphatases. This result indicates that the intracellular signals activated by the repellent effect involve a serine/threonine kinase pathway. Furthermore, the repellent effect of the EGF-L fragment for growth cones of cultured cerebellar neurons was also abolished by the identical modulators of serine/threonine kinase and -phosphatases. The inhibition of neurite outgrowth from hippocampal neurons by EGF-L was abolished in the presence of the serine threonine-kinase inhibitor H7. These results strongly suggest that the F3/tenascin-R interaction through EGF-L involves an intracellular activation of serine/ threonine kinase(s) in all F3-expressing cells tested.
Xiao
Z C
ZC
Department of Neurobiology, Swiss Federal Institute of Technology, Hönggerberg, Zürich.
Hillenbrand
R
R
Schachner
M
M
Thermes
S
S
Rougon
G
G
Gomez
S
S
D000818:Animals; D016466:CHO Cells / Q000737:chemistry / Q000187:drug effects / Q000201:enzymology; D015815:Cell Adhesion Molecules / Q000378:metabolism; D015816:Cell Adhesion Molecules, Neuronal / Q000378:metabolism*; D002531:Cerebellum / Q000166:cytology; D058966:Contactins; D006224:Cricetinae; D004815:Epidermal Growth Factor / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology; D051379:Mice; D016501:Neurites / Q000737:chemistry / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000201:enzymology / Q000648:ultrastructure; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D015290:Second Messenger Systems / Q000187:drug effects / Q000502:physiology*; D019063:Tenascin / Q000378:metabolism*; D014162:Transfection
D015815:Cell Adhesion Molecules; D015816:Cell Adhesion Molecules, Neuronal; D058966:Contactins; D019063:Tenascin; C074638:tenascin R; D004815:Epidermal Growth Factor; D011505:Protein-Tyrosine Kinases; D017346:Protein Serine-Threonine Kinases