 Pairwise binding between Jak3 mutants and villin showed that the FERM domain of Jak3 was sufficient for binding to P-villin with a Kd of 40.0 nM.However, the SH2 domain of Jak3 prevented P-villin from binding to the FERM domain of nonphosphorylated protein.The intramolecular interaction between the FERM and SH2 domains of nonphosphorylated Jak3 prevented Jak3 from binding to villin and tyrosine autophosphorylation of Jak3 at the SH2 domain decreased these intramolecular interactions and facilitated binding of the FERM domain to villin.