PMID- 10403832
OWN - NLM
STAT- MEDLINE
DCOM- 19990816
LR  - 20111117
IS  - 0006-291X (Print)
IS  - 0006-291X (Linking)
VI  - 260
IP  - 3
DP  - 1999 Jul 14
TI  - Insulin receptor substrate 4 supports insulin- and interleukin 4-stimulated 
      proliferation of hematopoietic cells.
PG  - 718-23
AB  - Signaling from the activated insulin receptor is initiated by its tyrosine 
      phosphorylation of the insulin receptor substrates (IRSs). The IRSs then act as 
      docking/effector proteins for various signaling proteins containing src homology 
      2 domains. Four members of the IRS family, designated IRS-1 through IRS-4, have 
      been identified. Although these IRSs show considerable structural homology, the 
      extent to which they overlap in functions has not been explored in detail. The 
      32D hematopoietic cell line, which contains no detectable amounts of any IRS, 
      provides a system in which to determine whether an IRS supports cell 
      proliferation. Previous studies have shown that introduction of IRS-1 or -2 into 
      32D cells overexpressing the insulin and IL-4 receptors (32D-R cells) enables the 
      cells to undergo mitogenesis in response to insulin and IL-4. In the present 
      study, we have examined IRS-4, a member of the IRS family that we recently 
      discovered, in this system. Expression of IRS-4 in 32D-R cells permitted the 
      cells to undergo mitogenesis and continuous proliferation in response to insulin 
      and IL-4. Immunoblotting of phosphotyrosine proteins showed that insulin and IL-4 
      elicited the tyrosine phosphorylation of IRS-4 in these cells. Thus, IRS-4, like 
      IRS-1 and -2, can function in the signal transduction pathways linking insulin 
      and IL-4 receptors to cell proliferation.
CI  - Copyright 1999 Academic Press.
FAU - Fantin, V R
AU  - Fantin VR
AD  - Department of Biochemistry, Dartmouth Medical School, Hanover, New Hampshire, 
      03755, USA.
FAU - Keller, S R
AU  - Keller SR
FAU - Lienhard, G E
AU  - Lienhard GE
FAU - Wang, L M
AU  - Wang LM
LA  - eng
GR  - DK42816/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (IRS1 protein, human)
RN  - 0 (IRS4 protein, human)
RN  - 0 (Insulin)
RN  - 0 (Insulin Receptor Substrate Proteins)
RN  - 0 (Irs1 protein, mouse)
RN  - 0 (Irs4 protein, mouse)
RN  - 0 (Phosphoproteins)
RN  - 0 (Receptors, Interleukin-4)
RN  - 207137-56-2 (Interleukin-4)
RN  - 21820-51-9 (Phosphotyrosine)
RN  - 9007-49-2 (DNA)
RN  - EC 2.7.10.1 (Receptor, Insulin)
SB  - IM
MH  - Adaptor Proteins, Signal Transducing
MH  - Animals
MH  - Blotting, Western
MH  - Cell Division/drug effects
MH  - Cell Line
MH  - DNA/biosynthesis
MH  - Hematopoietic System/*cytology/drug effects/metabolism
MH  - Humans
MH  - Insulin/*pharmacology
MH  - Insulin Receptor Substrate Proteins
MH  - Interleukin-4/*pharmacology
MH  - Mice
MH  - Molecular Weight
MH  - Phosphoproteins/genetics/*metabolism
MH  - Phosphorylation/drug effects
MH  - Phosphotyrosine/metabolism
MH  - Receptor, Insulin/genetics/metabolism
MH  - Receptors, Interleukin-4/genetics/metabolism
MH  - Signal Transduction/drug effects
MH  - Time Factors
MH  - Transfection
EDAT- 1999/07/15 00:00
MHDA- 1999/07/15 00:01
CRDT- 1999/07/15 00:00
PHST- 1999/07/15 00:00 [pubmed]
PHST- 1999/07/15 00:01 [medline]
PHST- 1999/07/15 00:00 [entrez]
AID - S0006-291X(99)90967-1 [pii]
AID - 10.1006/bbrc.1999.0967 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 1999 Jul 14;260(3):718-23. doi: 
      10.1006/bbrc.1999.0967.