Redox control of catalytic activities of membrane-associated protein tyrosine kinases.

Protein tyrosine kinases (PTKs) play key roles in starting the signal transduction network for cellular development and functions. A number of both receptor-type and non-receptor-type PTKs, which are normally at a resting state, are initially activated in association with functions of the cell membrane and membrane rafts. Results of recent studies have suggested that these membrane-associated mechanisms for activation of PTKs consist of the two steps that are under redox control. The first step is activation of cell surface receptors through chemical crosslinkage or aggregation of receptors and membrane rafts, which leads to production of reactive oxygen species (ROS) as second messengers of intracellular signal transduction. The second step involves chemical modification of PTKs at the highly conserved cysteine in the MXXCW motif as a global switch for starting the tyrosine phosphorylation-dependent local switch for activation of the catalytic activity of the enzyme.