Genome-Wide Gene Expression Analysis Identifies the Proto-oncogene Tyrosine-Protein Kinase Src as a Crucial Virulence Determinant of Infectious Laryngotracheitis Virus in Chicken Cells

Li, Hai; Wang, Fengjie; Han, Zongxi; Gao, Qi; Li, Huixin; Shao, Yuhao; Sun, Nana; Liu, Shengwang

It has been well documented in humans and mice that FAK and Src function mutually in integrin-mediated signaling: autophosphorylation of FAK at Tyr 397, which is stimulated by integrin, enables FAK to bind to the SH2 domain of Src, thereby resulting in the phosphorylation of Src at Tyr 416. The phosphorylation of Src at Tyr 416 in turn promotes the phosphorylation of FAK at Tyr 576 and Tyr 577 (57) (58) (59) (60) . To uncover the interaction between Src and FAK activation in our chicken model, the phosphorylation of Src at Tyr 416 and all three related FAK tyrosine residues was detected in detail. Consistent with the prior knowledge of Src and FAK in humans and mice, the phosphorylation of FAK at Tyr 576 and Tyr 577 upon ILTV infection in our model was dependent on Src activation ( Fig. 6B and C) , and the phosphorylation of Src at Tyr 416 by ILTV infection also required the phosphorylation of FAK (Fig. 6A) . However, the contribution of the phosphorylation of FAK at Tyr 397 to Src activation by ILTV in LMH cells is still unclear, because FAK is constitutively phosphorylated at Tyr 397 and is unaffected by ILTV infection (Fig. 6A) . The basal activity of Src is also essential for the maintenance of the constitutive phosphorylation of FAK at Tyr 397 (Fig. 6A ). Further investigation of the basal level of phosphorylation of FAK at Tyr 397, as well as its contribution to Src activation by ILTV in chicken cells in which FAK Tyr 397 is mutated, is required to answer this question.