Non-receptor Tyrosine Kinases Regulate The Functions Of EEF2 And G?₁₃ Through Tyrosine Phosphorylation

Non-receptor tyrosine kinases phosphorylate proteins at tyrosine residues. Among them, the Src-family kinases and Abl-family kinases are the most well studied. Non-receptor tyrosine kinases can transmit signals from membrane receptors, including RTKs (Receptor Tyrosine Kinases), GPCRs (G Protein-Coupled Receptors) and Integrin. They regulate cell proliferation, cell migration, cell survival and other functions. Mis-regulation of non-receptor tyrosine kinases could cause cancer.Here we study the functions of two non-receptor tyrosine kinases. The first is Csk (C-terminal Src Kinase), known as a suppressor of the Src-family kinases through phosphorylation. We report that Csk can interact with eEF2 (Eukaryotic Elongation Factor 2) and phosphorylate eEF2. This phosphorylation can lead to proteolytic cleavage of eEF2. We also find that eEF2 can be SUMOylated, and SUMOylation could crosstalk with phosphorylation. These two translational modifications of eEF2 promote its cleavage. The produced small fragment can induce nuclear morphological changes and aneuploidy, similar to those observed in cancer cells.We also report that another non-receptor tyrosine kinase, Abl, can interact with G-protein (Heterotrimeric-Guanine-Nucleotide-Binding Protein) G?13. Abl and G?13 could co-localize on dorsal ruffles and lamellipodia in migrating cells after PDGF (Platelet-Derived Growth Factor) stimulation. G?13 could be phosphorylated by Abl. Phosphorylated G?13 then is translocated to cytosol. However, phosphorylation of G?13 had no effect on the G?13-RhoA signaling. Furthermore we observe that Abl could induce the interaction of G?13 and EPLIN (epithelial protein lost in neoplasm), a protein that can stabilize actin filaments. These studies will illustrate the function of G?13 and Abl in cell migration.