Control of Genetically Prescribed Protein Tyrosine Kinase Activities by Environment-Linked Redox Reactions

Figure 2

Summary of observations for bi-directional control of PTKs through their potential structural modification by redox reactions. Kemble and Sun demonstrated a pathway for definitive structural modification-mediated downregulation of the kinase activity of Src in heavily oxidative environments in vitro through disulfide-bonded dimerization of Src proteins at Cys277. On the other hand, Kato et al. and Takeda et al. revealed another pathway for possibly fine structural modification-mediated upregulation of kinase activities of RET-PTC-1 in a mildly oxidative environment in vivo through disulfide-bonded dimerization of RET proteins at Cys376. Pu et al. and Akhand et al. further demonstrated that exposure of immunoprecipitated Src proteins from cell lysates to low to moderate levels of sulfhydryl-reactive Hg²⁺ or NO-releasing SNAP induced Tyr527/PTP-independent activation of Src kinase, whereas their exposure to a high level of Hg²⁺ downregulated it.