Tyro3 carboxyl terminal region confers stability and contains the autophosphorylation sites

Tyro3, a member of TAM receptor tyrosine kinase family has been suggested to be autophosphorylated upon activation. In the current study we mapped the autophosphorylation sites of murine Tyro3 to tyrosine 723 and 756, with K540 being required for its kinase activity. Knockdown of Axl significantly decreases the tyrosyl-phosphorylation of Tyro3 in fibroblasts NR6WT, suggesting an interaction among the TAM family members. Interestingly, the carboxyl terminal region of Tyro3 is required for its stability in cells with a minimal length of 1-778 amino acids which is not conserved in murine Axl, a member of TAM. These data suggest that the autophosphorylation sites of TAM RTK members are unique although they share high similarity in amino acids within their carboxyl kinase domain.