PMID- 10051596
OWN - NLM
STAT- MEDLINE
DCOM- 19990415
LR  - 20190501
IS  - 0027-8424 (Print)
IS  - 0027-8424 (Linking)
VI  - 96
IP  - 5
DP  - 1999 Mar 2
TI  - The conserved SOCS box motif in suppressors of cytokine signaling binds to
      elongins B and C and may couple bound proteins to proteasomal degradation.
PG  - 2071-6
AB  - The suppressors of cytokine signaling (SOCS) family of proteins act as
      intracellular inhibitors of several cytokine signal transduction pathways. Their 
      expression is induced by cytokine activation of the Janus kinase/signal
      transducer and activator of transcription (JAK/STAT) pathway and they act as a
      negative feedback loop by subsequently inhibiting the JAK/STAT pathway either by 
      direct interaction with activated JAKs or with the receptors. These interactions 
      are mediated at least in part by the SH2 domain of SOCS proteins but these
      proteins also contain a highly conserved C-terminal homology domain termed the
      SOCS box. Here we show that the SOCS box mediates interactions with elongins B
      and C, which in turn may couple SOCS proteins and their substrates to the
      proteasomal protein degradation pathway. Analogous to the family of
      F-box-containing proteins, it appears that the SOCS proteins may act as adaptor
      molecules that target activated cell signaling proteins to the protein
      degradation pathway.
FAU - Zhang, J G
AU  - Zhang JG
AD  - Walter and Eliza Hall Institute of Medical Research and the Cooperative Research 
      Centre for Cellular Growth Factors, P.O. Royal Melbourne Hospital, Victoria 3050,
      Australia.
FAU - Farley, A
AU  - Farley A
FAU - Nicholson, S E
AU  - Nicholson SE
FAU - Willson, T A
AU  - Willson TA
FAU - Zugaro, L M
AU  - Zugaro LM
FAU - Simpson, R J
AU  - Simpson RJ
FAU - Moritz, R L
AU  - Moritz RL
FAU - Cary, D
AU  - Cary D
FAU - Richardson, R
AU  - Richardson R
FAU - Hausmann, G
AU  - Hausmann G
FAU - Kile, B T
AU  - Kile BT
FAU - Kent, S B
AU  - Kent SB
FAU - Alexander, W S
AU  - Alexander WS
FAU - Metcalf, D
AU  - Metcalf D
FAU - Hilton, D J
AU  - Hilton DJ
FAU - Nicola, N A
AU  - Nicola NA
FAU - Baca, M
AU  - Baca M
LA  - eng
GR  - R01 CA022556/CA/NCI NIH HHS/United States
GR  - R37 CA022556/CA/NCI NIH HHS/United States
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  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Carrier Proteins)
RN  - 0 (Cytokines)
RN  - 0 (Elongin)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Multienzyme Complexes)
RN  - 0 (Proteins)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Repressor Proteins)
RN  - 0 (SOCS1 protein, human)
RN  - 0 (SOCS3 protein, human)
RN  - 0 (Socs1 protein, mouse)
RN  - 0 (Socs3 protein, mouse)
RN  - 0 (Suppressor of Cytokine Signaling 1 Protein)
RN  - 0 (Suppressor of Cytokine Signaling 3 Protein)
RN  - 0 (Suppressor of Cytokine Signaling Proteins)
RN  - 0 (Transcription Factors)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 3.4.22.- (Cysteine Endopeptidases)
RN  - EC 3.4.25.1 (Proteasome Endopeptidase Complex)
SB  - IM
EIN - Proc Natl Acad Sci U S A. 2015 Jun 2;112(22):E2979. Kile, B J [corrected to Kile,
      Benjamin T]. PMID: 25956176
MH  - Amino Acid Sequence
MH  - Animals
MH  - Binding Sites
MH  - Carrier Proteins/chemistry/*metabolism
MH  - Cell Line
MH  - Cysteine Endopeptidases/*metabolism
MH  - Cytokines/*physiology
MH  - Elongin
MH  - Humans
MH  - *Intracellular Signaling Peptides and Proteins
MH  - Mice
MH  - Models, Chemical
MH  - Molecular Sequence Data
MH  - Multienzyme Complexes/*metabolism
MH  - Proteasome Endopeptidase Complex
MH  - Protein-Tyrosine Kinases/*metabolism
MH  - Proteins/chemistry/*metabolism
MH  - Recombinant Fusion Proteins/biosynthesis
MH  - Recombinant Proteins/metabolism
MH  - *Repressor Proteins
MH  - Signal Transduction
MH  - Suppressor of Cytokine Signaling 1 Protein
MH  - Suppressor of Cytokine Signaling 3 Protein
MH  - Suppressor of Cytokine Signaling Proteins
MH  - Transcription Factors/*metabolism
MH  - Transfection
MH  - Tumor Cells, Cultured
MH  - src Homology Domains
PMC - PMC26738
EDAT- 1999/03/03 00:00
MHDA- 1999/03/03 00:01
CRDT- 1999/03/03 00:00
PHST- 1999/03/03 00:00 [pubmed]
PHST- 1999/03/03 00:01 [medline]
PHST- 1999/03/03 00:00 [entrez]
AID - 10.1073/pnas.96.5.2071 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 1999 Mar 2;96(5):2071-6. doi: 10.1073/pnas.96.5.2071.