Impaired neurite outgrowth of src-minus cerebellar neurons on the cell adhesion molecule L1.
The nonreceptor tyrosine protein kinases pp60c-src, p59fyn, and pp62c-yes are localized in growth cones of developing neurons, but their function is undefined. To determine whether these tyrosine kinases were capable of regulating substrate-dependent axon growth, cultures of cerebellar neurons from wild-type, src-, fyn-, and yes- mice were analyzed for neurite outgrowth on the neural cell adhesion molecule L1 or the extracellular matrix protein laminin. The rate of neurite extension on L1 was reduced in src-, but not in fyn- or yes- neurons. Neurite extension on laminin was unaltered in src-, fyn-, or yes- neurons, indicating that pp60c-src, p59fyn, or pp62c-yes is not likely to participate in integrin-dependent axon growth. These results demonstrate that pp60c-src is a component of the intracellular signaling pathway in L1-mediated axonal growth and suggest that Src-related nonreceptor tyrosine kinases may have distinct, nonredundant functions in the nervous system.
Ignelzi
M A
MA
Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill 27599-7260.
Miller
D R
DR
Soriano
P
P
Maness
P F
PF
D000818:Animals; D015816:Cell Adhesion Molecules, Neuronal / Q000502:physiology*; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology*; D015151:Immunoblotting; D007797:Laminin / Q000502:physiology; D039841:Leukocyte L1 Antigen Complex; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D016501:Neurites / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D010766:Phosphorylation; D019000:Phosphotyrosine; D011505:Protein-Tyrosine Kinases / Q000502:physiology*; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000502:physiology*; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
D015816:Cell Adhesion Molecules, Neuronal; D007797:Laminin; D039841:Leukocyte L1 Antigen Complex; D019000:Phosphotyrosine; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; D016392:Proto-Oncogene Proteins pp60(c-src)