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

XP Chen, JA Losman, S Cowan, E Donahue, S Fay, BQ Vuong, MC Nawijn, D Capece, VL Cohan, P Rothman*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

157 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)2175-2180
Number of pages6
JournalProceedings of the National Academy of Science of the United States of America
Volume99
Issue number4
DOIs
Publication statusPublished - 19-Feb-2002

Keywords

  • INTERFERON-GAMMA
  • GENE-EXPRESSION
  • SIGNAL-TRANSDUCTION
  • BOX MOTIF
  • V-ABL
  • ACTIVATION
  • INHIBITOR
  • DEFICIENT
  • CYTOKINE
  • CELLS

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