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

X. Peter Chen; Julie A. Losman; Simone Cowan; Elizabeth Donahue; Scott Fay; Bao Q. Vuong; Martijn C. Nawijn; Danielle Capece; Victoria L. Cohan; Paul Rothman

doi:10.1073/pnas.042035699

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

X. Peter Chen, Julie A. Losman, Simone Cowan, Elizabeth Donahue, Scott Fay, Bao Q. Vuong, Martijn C. Nawijn, Danielle Capece, Victoria L. Cohan, Paul Rothman

Research output: Contribution to journal › Article › peer-review

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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 language	English (US)
Pages (from-to)	2175-2180
Number of pages	6
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	99
Issue number	4
DOIs	https://doi.org/10.1073/pnas.042035699
State	Published - Feb 19 2002
Externally published	Yes

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title = "Pim serine/threonine kinases regulate the stability of Socs-1 protein",

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.",

author = "Chen, {X. Peter} and Losman, {Julie A.} and Simone Cowan and Elizabeth Donahue and Scott Fay and Vuong, {Bao Q.} and Nawijn, {Martijn C.} and Danielle Capece and Cohan, {Victoria L.} and Paul Rothman",

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doi = "10.1073/pnas.042035699",

language = "English (US)",

volume = "99",

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journal = "Proceedings of the National Academy of Sciences of the United States of America",

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T1 - Pim serine/threonine kinases regulate the stability of Socs-1 protein

AU - Chen, X. Peter

AU - Losman, Julie A.

AU - Cowan, Simone

AU - Donahue, Elizabeth

AU - Fay, Scott

AU - Vuong, Bao Q.

AU - Nawijn, Martijn C.

AU - Capece, Danielle

AU - Cohan, Victoria L.

AU - Rothman, Paul

PY - 2002/2/19

Y1 - 2002/2/19

N2 - 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.

AB - 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.

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U2 - 10.1073/pnas.042035699

DO - 10.1073/pnas.042035699

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SN - 0027-8424

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JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

IS - 4

ER -

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

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