PMID- 10551777
OWN - NLM
STAT- MEDLINE
DCOM- 19991130
LR  - 20121115
IS  - 0888-8809 (Print)
IS  - 0888-8809 (Linking)
VI  - 13
IP  - 11
DP  - 1999 Nov
TI  - Mechanism of inhibition of growth hormone receptor signaling by suppressor of
      cytokine signaling proteins.
PG  - 1832-43
AB  - In this study we have investigated the role of suppressor of cytokine signaling
      (SOCS) proteins in GH receptor-mediated signaling. GH-induced transcription was
      inhibited by SOCS-1 and SOCS-3, while SOCS-2 and cytokine inducible
      SH2-containing protein (CIS) had no effect By using chimeric SOCS proteins it was
      found that the ability of SOCS proteins to inhibit GH-mediated transcription was 
      located in the amino-terminal 40-80 amino acids. In SOCS-3, 46 amino acids
      C-terminal to the SH2 domain were required for the inhibitory activity, while a
      truncated SOCS-1 having only 2 amino acids C-terminal to the SH2 domain was able 
      to inhibit GH-mediated transcription. Both SOCS-1 and SOCS-3 were able to inhibit
      GH-induced STAT5 (signal transducer and activator of transcription) activation.
      SOCS-1 inhibited the tyrosine kinase activity of Janus kinase 2 (JAK2) directly, 
      while SOCS-3 only inhibited JAK2 when stimulated by the GH receptor. All four
      SOCS proteins were able to bind to a tyrosine-phosphorylated
      glutathione-S-transferase-GH receptor fusion protein, and SOCS-3 required the
      same 46 C-terminal amino acids for GH receptor binding as it did for inhibition
      of GH-mediated transcription and STAT5 activation. These data suggest that SOCS-1
      and -3 can suppress GH-induced transcriptional activity, presumably by inhibiting
      the kinase activity of JAK2 either directly in the case of SOCS-1 or via binding 
      to the tyrosine-phosphorylated GH receptor in the case of SOCS-3.
FAU - Hansen, J A
AU  - Hansen JA
AD  - Hagedorn Research Institute, Gentofte, Denmark.
FAU - Lindberg, K
AU  - Lindberg K
FAU - Hilton, D J
AU  - Hilton DJ
FAU - Nielsen, J H
AU  - Nielsen JH
FAU - Billestrup, N
AU  - Billestrup N
LA  - eng
GR  - CA-22556/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Mol Endocrinol
JT  - Molecular endocrinology (Baltimore, Md.)
JID - 8801431
RN  - 0 (Carrier Proteins)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Milk Proteins)
RN  - 0 (Proteins)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Receptors, Somatotropin)
RN  - 0 (STAT5 Transcription Factor)
RN  - 0 (Trans-Activators)
RN  - 9002-72-6 (Growth Hormone)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.10.2 (Janus Kinase 2)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - CHO Cells/metabolism
MH  - Carrier Proteins/*metabolism
MH  - Cricetinae
MH  - DNA-Binding Proteins/genetics/metabolism
MH  - Growth Hormone/metabolism/pharmacology
MH  - Janus Kinase 2
MH  - *Milk Proteins
MH  - Molecular Sequence Data
MH  - Phosphorylation
MH  - Protein-Tyrosine Kinases/metabolism
MH  - Proteins/*metabolism
MH  - *Proto-Oncogene Proteins
MH  - Receptors, Somatotropin/*metabolism
MH  - STAT5 Transcription Factor
MH  - Signal Transduction
MH  - Trans-Activators/genetics/metabolism
MH  - Transcription, Genetic
MH  - src Homology Domains
EDAT- 1999/11/07 00:00
MHDA- 1999/11/07 00:01
CRDT- 1999/11/07 00:00
PHST- 1999/11/07 00:00 [pubmed]
PHST- 1999/11/07 00:01 [medline]
PHST- 1999/11/07 00:00 [entrez]
AID - 10.1210/mend.13.11.0368 [doi]
PST - ppublish
SO  - Mol Endocrinol. 1999 Nov;13(11):1832-43. doi: 10.1210/mend.13.11.0368.