Protein tyrosine kinases in malignant melanoma

Protein tyrosyl phosphorylation is an essential component in intracellular signalling, with diverse and crucial functions including mediation of cell proliferation, survival, death, differentiation, migration and attachment. It is regulated by the balance between the activities of protein tyrosine k inases (PTKs) and protein tyrosine phosphatases. A number of PTKs are encod ed by proto-oncogenes or viral oncogenes, and are thus strongly implicated in cancer. While a role for PTKs in human melanoma is less firmly establish ed, human melanomas or melanoma cells have been reported to contain more ty rosine phosphate than normal melanocytes, and some receptor PTKs (EPH-A2/ E CK and EPH-B3) are overexpressed in over 90% of melanoma cell lines. Other specific PTKs are also frequently overexpressed, including KDR and fibrobla st growth factor receptor-4 (FGF-R4), while, interestingly, yet others, suc h as KIT and FES, are consistently downregulated in melanoma cell lines. Al l of these differentially expressed PTKs are candidates for gene products i mportant in melanoma development. In addition, PTKs expressed in significan t amounts in both benign and malignant melanocytes, such as insulin-like gr owth factor-1 receptor (IGF1-R), FGF-R1, HEP2/NEU and FAK, are likely to pl ay a role in melanoma genesis and progression. (C) 2000 Lippincott Williams & Wilkins.