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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Carrier Proteins / chemistry*
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Carrier Proteins / metabolism*
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Cell Line
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Cloning, Molecular
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DNA, Complementary / metabolism
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Gene Library
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Glutathione Transferase / metabolism
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Humans
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Interleukin-4 / metabolism
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Intracellular Signaling Peptides and Proteins*
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Luciferases / metabolism
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Mice
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Phosphorylation
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Plasmids
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Precipitin Tests
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Protein Binding
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Protein Serine-Threonine Kinases
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Proto-Oncogene Proteins / genetics*
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Proto-Oncogene Proteins / physiology*
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Proto-Oncogene Proteins c-pim-1
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RNA, Messenger / metabolism
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Recombinant Fusion Proteins / metabolism
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Repressor Proteins*
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STAT6 Transcription Factor
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Signal Transduction
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Suppressor of Cytokine Signaling 1 Protein
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Suppressor of Cytokine Signaling Proteins
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Thymus Gland / cytology
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Thymus Gland / metabolism
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Time Factors
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Trans-Activators / metabolism
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Transfection
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Two-Hybrid System Techniques
Substances
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Carrier Proteins
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DNA, Complementary
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Intracellular Signaling Peptides and Proteins
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Proto-Oncogene Proteins
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RNA, Messenger
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Recombinant Fusion Proteins
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Repressor Proteins
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SOCS1 protein, human
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STAT6 Transcription Factor
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STAT6 protein, human
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Socs1 protein, mouse
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Stat6 protein, mouse
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Suppressor of Cytokine Signaling 1 Protein
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Suppressor of Cytokine Signaling Proteins
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Trans-Activators
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Interleukin-4
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Luciferases
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Glutathione Transferase
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Protein Serine-Threonine Kinases
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Proto-Oncogene Proteins c-pim-1
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proto-oncogene proteins pim