UV Irradiation and Superactivation

Science's STKE  15 Feb 2000:
Vol. 2000, Issue 19, pp. tw6
DOI: 10.1126/stke.2000.19.tw6

UV irradiation damages DNA and can promote oncogenesis. Kato et al. now show that UV light can further affect already oncogenic, contitutively active tyrosine kinases at the cell surface by superactivating them. The c-Ret proto-oncogene is a receptor-type tyrosine kinase, and constitutively activated forms have been associated with certain cancers. The study shows that when cells expressing c-Ret or the activated receptor forms are exposed to UV light, there is an increase in receptor dimerization and activation, and an increase in overall cell phosphorylation. A cysteine residue in one of the intracellular kinase domains was critical for disulfide bond formation and dimerization. Expression of a superoxide dismutase, which scavenges free radicals, counteracted the UV effect. Thus, UV light can activate and superactivate Ret by changing cellular redox levels to oxidative, thereby promoting disulfide bond-mediated dimerization of Ret.

Kato, M., Iwashita, T., Takeda, K., Akhand, A.A., Liu, W., Yoshihara, M., Asai, N., Suzuki, H., Takahashi, M., and Nakashima, I. (2000) Ultraviolet light induces redox teaction-mediated dimerization and superactivation of oncogenic Ret tyrosine kinases. Mol. Biol. Cell 11: 93-101. [Abstract] [Full Text]