PMID- 10514492
OWN - NLM
STAT- MEDLINE
DCOM- 19991119
LR  - 20190508
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 42
DP  - 1999 Oct 15
TI  - The role of SOCS-3 in leptin signaling and leptin resistance.
PG  - 30059-65
AB  - We earlier demonstrated that leptin induces expression of SOCS-3 mRNA in the
      hypothalamus. Furthermore, transfection data suggest that SOCS-3 is an inhibitor 
      of leptin signaling. However, little is known about the regulation of SOCS-3
      expression by leptin and the mechanism by which SOCS-3 inhibits leptin action. We
      here show that in CHO cells stably expressing the long form of the leptin
      receptor (CHO-OBRl), leptin induces transient expression of endogenous SOCS-3
      mRNA but not of CIS, SOCS-1, or SOCS-2 mRNA. SOCS-3 protein levels were maximal
      after 2-3 h of leptin treatment and remained elevated at 20 h. Furthermore, in
      leptin-pretreated CHO-OBRl cells, proximal leptin signaling was blocked for more 
      than 20 h after pretreatment, thus correlating with increased SOCS-3 expression. 
      Leptin pretreatment did not affect cell surface expression of leptin receptors as
      measured by (125)I-leptin binding assays. In transfected COS cells, forced
      expression of SOCS-3 results in inhibition of leptin-induced tyrosine
      phosphorylation of JAK2. Finally, JAK2 co-immunoprecipitates with SOCS-3 in
      lysates from leptin-treated COS cells. These results suggest that SOCS-3 is a
      leptin-regulated inhibitor of proximal leptin signaling in vivo. Excessive SOCS-3
      activity in leptin-responsive cells is therefore a potential mechanism for leptin
      resistance, a characteristic feature in human obesity.
FAU - Bjorbaek, C
AU  - Bjorbaek C
AD  - Department of Medicine, Division of Endocrinology, Beth Israel Deaconess Medical 
      Center, Harvard Medical School, Boston, Massachusetts 02215, USA.
FAU - El-Haschimi, K
AU  - El-Haschimi K
FAU - Frantz, J D
AU  - Frantz JD
FAU - Flier, J S
AU  - Flier JS
LA  - eng
GR  - DK R37 28082/DK/NIDDK 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  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Carrier Proteins)
RN  - 0 (Leptin)
RN  - 0 (Proteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Cell Surface)
RN  - 0 (Receptors, Leptin)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Repressor Proteins)
RN  - 0 (SOCS3 protein, human)
RN  - 0 (Suppressor of Cytokine Signaling 3 Protein)
RN  - 0 (Suppressor of Cytokine Signaling Proteins)
RN  - 0 (Transcription Factors)
RN  - 0 (leptin receptor, human)
SB  - IM
MH  - Animals
MH  - CHO Cells
MH  - Carrier Proteins/genetics
MH  - Cricetinae
MH  - Gene Expression Regulation/physiology
MH  - Humans
MH  - Leptin/*physiology
MH  - Proteins/genetics/*physiology
MH  - RNA, Messenger/genetics
MH  - *Receptors, Cell Surface
MH  - Receptors, Leptin
MH  - Recombinant Proteins/metabolism
MH  - *Repressor Proteins
MH  - Signal Transduction/*physiology
MH  - Suppressor of Cytokine Signaling 3 Protein
MH  - Suppressor of Cytokine Signaling Proteins
MH  - *Transcription Factors
EDAT- 1999/10/09 00:00
MHDA- 1999/10/09 00:01
CRDT- 1999/10/09 00:00
PHST- 1999/10/09 00:00 [pubmed]
PHST- 1999/10/09 00:01 [medline]
PHST- 1999/10/09 00:00 [entrez]
AID - 10.1074/jbc.274.42.30059 [doi]
PST - ppublish
SO  - J Biol Chem. 1999 Oct 15;274(42):30059-65. doi: 10.1074/jbc.274.42.30059.