Pim serine/threonine kinases regulate the stability of Socs-1 protein.
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.
Chen
X Peter
XP
Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
Losman
Julie A
JA
Cowan
Simone
S
Donahue
Elizabeth
E
Fay
Scott
S
Vuong
Bao Q
BQ
Nawijn
Martijn C
MC
Capece
Danielle
D
Cohan
Victoria L
VL
Rothman
Paul
P
D000818:Animals; D002352:Carrier Proteins / Q000737:chemistry* / Q000378:metabolism*; D002460:Cell Line; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000378:metabolism; D015723:Gene Library; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D015847:Interleukin-4 / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins; D008156:Luciferases / Q000378:metabolism; D051379:Mice; D010766:Phosphorylation; D010957:Plasmids; D011233:Precipitin Tests; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000502:physiology*; D051573:Proto-Oncogene Proteins c-pim-1; D012333:RNA, Messenger / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012097:Repressor Proteins; D050800:STAT6 Transcription Factor; D015398:Signal Transduction; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D013950:Thymus Gland / Q000166:cytology / Q000378:metabolism; D013997:Time Factors; D015534:Trans-Activators / Q000378:metabolism; D014162:Transfection; D020798:Two-Hybrid System Techniques
D002352:Carrier Proteins; D018076:DNA, Complementary; D047908:Intracellular Signaling Peptides and Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; C108944:SOCS1 protein, human; D050800:STAT6 Transcription Factor; C494101:STAT6 protein, human; C491590:Socs1 protein, mouse; C494100:Stat6 protein, mouse; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D015534:Trans-Activators; D015847:Interleukin-4; D008156:Luciferases; D005982:Glutathione Transferase; D017346:Protein Serine-Threonine Kinases; D051573:Proto-Oncogene Proteins c-pim-1; C406031:proto-oncogene proteins pim