Pim serine/threonine kinases regulate the stability of Socs-1 protein

XP Chen, JA Losman, S Cowan… - Proceedings of the …, 2002 - National Acad Sciences
XP Chen, JA Losman, S Cowan, E Donahue, S Fay, BQ Vuong, MC Nawijn, D Capece…
Proceedings of the National Academy of Sciences, 2002National Acad Sciences
Studies of SOCS-1-deficient mice have implicated Socs-1 in the suppression of JAK-STAT
(Janus tyrosine kinase-signal transducers and activators of transcription) signaling and T
cell development. It has been suggested that the levels of Socs-1 protein may be regulated
through the proteasome pathway. Here we show that Socs-1 interacts with members of the
Pim family of serine/threonine kinases in thymocytes. Coexpression of the Pim kinases with
Socs-1 results in phosphorylation and stabilization of the Socs-1 protein. The protein levels …
Studies of SOCS-1-deficient mice have implicated Socs-1 in the suppression of JAK-STAT (Janus tyrosine kinase-signal transducers and activators of transcription) signaling and T cell development. It has been suggested that the levels of Socs-1 protein may be regulated through the proteasome pathway. Here we show that Socs-1 interacts with members of the Pim family of serine/threonine kinases in thymocytes. Coexpression of the Pim kinases with Socs-1 results in phosphorylation and stabilization of the Socs-1 protein. The protein levels of Socs-1 are significantly reduced in the Pim-1−/−, Pim-2−/− mice as compared with wild-type mice. Similar to Socs-1−/− mice, thymocytes from Pim-1−/−, Pim-2−/− mice showed prolonged Stat6 phosphorylation upon IL-4 stimulation. These data suggest that the Pim kinases may regulate cytokine-induced JAK-STAT signaling through modulation of Socs-1 protein levels.
National Acad Sciences