Authors: | Loganzo, F. Jr; Dosik, J. S.; Zhao, Y.; Vidal, M. J.; Nanus, D. M.; Sudol, M.; Albino, A. P. |
Article Title: | Elevated expression of protein tyrosine kinase c-Yes, but not c-Src, in human malignant melanoma |
Abstract: | The c-yes proto-oncogene encodes a protein tyrosine kinase, p62(c-yes) (c-Yes) that belongs to the Src family of non-receptor type protein tyrosine kinases. We compared the levels of c-Yes kinase activity and protein by immune complex kinase assays and immune blot analysis in 20 human melanoma and 10 human melanocyte cell lines. Results show that the average kinase activity of c-Yes in most melanoma cell lines is 5-10-fold higher than that in melanocyte cell lines. The protein level of c-Yes in these melanoma cell lines is correspondingly higher than that in melanocytes. The increase in c-Yes kinase activity is most likely attributable to the elevated protein level because single-strand conformational polymorphism of all structural and functional domains detected no mutations in any of the c-yes coding regions. Subcellular fractionation analysis indicated that c-Yes localizes to the plasma membrane, perinuclear and cytosolic compartments while c-Src predominantly associates with plasma membranes. In melanoma cells in which an elevated level of c-Yes is observed, a protein of 39 kD is heavily phosphorylated on tyrosine. This protein is only observed in melanoma cells and not in melanocytes, suggesting a perturbed signaling pathway in melanoma cells that results in abnormal tyrosine phosphorylation of cellular proteins. These data suggest that derangement of expression of the c-Yes tyrosine kinase may have a role in the malignant progression of the human melanocyte. |
Keywords: | signal transduction; clinical article; controlled study; protein phosphorylation; human cell; proto-oncogene proteins; proto oncogene; melanoma; gene expression; melanocyte; melanocytes; cell line; tumor cells, cultured; enzyme activity; protein tyrosine kinase; tyrosine; phosphorylation; cell transformation, neoplastic; blotting, western; rna, messenger; immunoblotting; cellular distribution; immunoassay; dna mutational analysis; single stranded dna; protein determination; dna polymorphism; tetradecanoylphorbol acetate; proto-oncogenes; oncogene src; protein content; protein-tyrosine kinase; cell oncogene; human; priority journal; article; support, u.s. gov't, p.h.s.; proto-oncogene protein pp60(c-src) |
Journal Title: | Oncogene |
Volume: | 8 |
Issue: | 10 |
ISSN: | 0950-9232 |
Publisher: | Nature Publishing Group |
Date Published: | 1993-10-01 |
Start Page: | 2637 |
End Page: | 2644 |
Language: | English |
PUBMED: | 7690926 |
PROVIDER: | scopus |
DOI/URL: | |
Notes: | Article -- Export Date: 1 March 2019 -- Source: Scopus |