In humans, activated PTK6 (BRK) phosphorylates STAT3 on tyrosine residue Y705. PTK6-mediated phosphorylation of STAT3 is promoted by STAP2 and inhibited by SOCS3 (Liu et al. 2006, Ikeda et al. 2010).In mouse, Ptk6-mediated phosphorylation of Stat3 is promoted by Stap2 and inhibited by Socs3. Heme oxygenase-1 (Hmox1) binds to tyrosine-705 and three domains on Stat3 (DNA-binding, linker, and transactivation domains), directly regulating Stat3 activation. Additionally it co-inhibits Socs3, a negative feedback factor of Stat3 activation, as well as RORγt, thereby decreasing Th2 and Th17 immune responses, and alleviating airway inflammation (Lin et al, 2020; Lin et al, 2017).
Reich, NC, Gao, Y, Poli, V, Miller, WT, Liu, L, Qiu, H
Miyasaka, Y, Matsuda, T, Mizushima, A, Nanbo, A, Ikeda, O, Sekine, Y, Nakasuji, M, Muromoto, R, Yamamoto, C, Yoshimura, A, Oritani, K
protein tyrosine kinase activity of p-Y342-PTK6:p-Y250-STAP2:STAT3 [cytosol]
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