Tyrosine kinase 2 interacts with the proapoptotic protein Siva-1 and augments its apoptotic functions.
Siva-1 is a molecule that has the potential to induce both extrinsic (receptor-mediated) and intrinsic (non-receptor-mediated) apoptosis. Siva-1 binds to CD27, a member of the tumor necrosis factor receptor (TNFR) family, Abl-related gene (ARG), and BCL-X(L), and these partner molecules reportedly enhance the apoptotic properties of Siva-1. In this study, we show that Siva-1 also interacts with a member of the Jak family protein kinases, tyrosine kinase 2 (Tyk2). Siva-1 bound to Tyk2 via its N-terminal region, and Tyk2 phosphorylated Siva-1 at tyrosines 53 and 162. In murine pro-B cells, Ba/F3 cells, expression of Tyk2 augmented Siva-1-induced apoptosis. This augmentation of Siva-1-induced apoptosis was retained regardless of the phosphorylation of Siva-1, but was almost completely prevented by the abrogation of the Tyk2-Siva-1 association. These findings indicate that the interaction between Siva-1 and Tyk2 directly augments the apoptotic activity of Siva-1. Our novel observations suggest that Siva-1 forms a functional complex with Tyk2 and participates in the transduction of signals that inhibit B lymphocyte growth.
Shimoda
Haruko K
HK
Gastroenterology and Hematology, Faculty of Medicine, Miyazaki University, 5200 Kihara, Kiyotake, Miyazaki 889-1692, Japan. hshimoda@fc.miyazaki-u.ac.jp
Shide
Kotaro
K
Kameda
Takuro
T
Matsunaga
Takuya
T
Shimoda
Kazuya
K
D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism*; D001402:B-Lymphocytes / Q000378:metabolism / Q000502:physiology*; D002460:Cell Line; D006801:Humans; D010766:Phosphorylation; D017434:Protein Structure, Tertiary; D053634:TYK2 Kinase / Q000378:metabolism*; D020798:Two-Hybrid System Techniques; D014443:Tyrosine / Q000235:genetics / Q000378:metabolism
D051017:Apoptosis Regulatory Proteins; C106549:SIVA1 protein, human; D014443:Tyrosine; D053634:TYK2 Kinase