Tyrosine phosphorylation
In the summer of 1979, studies of polyomavirus middle T and v-Src associated kinase activities led to the discovery of tyrosine phosphorylation as a new type of protein modification.
The recruitment of SH2 domain proteins to autophosphorylated RTKs at the plasma membrane is essential for initiating and propagating downstream signaling.
[9] Phosphorylation on tyrosine residues, which are localized on membrane proteins, stimulates a cascade of signaling pathways that control cell proliferation, migration, and adhesion.
[10] Tyrosine phosphorylation mediates in signal transduction pathways during germ cell development and determines their association with the differentiation of a functional gamete.
One of these cases is tyrosine phosphorylation of caveolin 2 (Cav-2) that negatively regulates the anti-proliferative function of transforming growth factor beta (TGF-beta) in endothelial cells.
Phosphorylation of selected tyrosine sites on receptor substrates is known to activate different pathways leading to increased glucose uptake, lipogenesis, and glycogen and protein synthesis, as well as to the stimulation of cell growth.
In addition to the activation of these pathways by tyrosine phosphorylation, several mechanisms of downregulating the response to insulin stimulation have also been identified.
[16] Many studies demonstrating high levels of protein-tyrosine kinases and phosphatases in the central nervous system have suggested that tyrosine phosphorylation is also involved in the regulation of neuronal processes.
High levels of protein-tyrosine kinases and phosphatases and their substrates at synapses, both presynaptically and postsynaptically, suggest that tyrosine phosphorylation may regulate synaptic transmission.
The role of tyrosine phosphorylation in the regulation of ligand-gated ion channels in the central nervous system has been less clear.
Changes in tyrosine kinase activity are implicated in numerous human diseases, including cancers, diabetes, and pathogen infectivity.
Understanding the mechanism of CD4-mediated negative signaling is of particular interest in view of the progressive depletion of the CD4+ subset of T lymphocytes by the human immunodeficiency virus (HIV), which causes AIDS.
