PMID- 10531310
OWN - NLM
STAT- MEDLINE
DCOM- 19991216
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 44
DP  - 1999 Oct 29
TI  - Insulin receptor substrate-4 enhances insulin-like growth factor-I-induced cell 
      proliferation.
PG  - 31179-84
AB  - The insulin receptor substrates (IRSs)-1-4 play important roles in signal 
      transduction emanating from the insulin and insulin-like growth factor (IGF)-I 
      receptors. IRS-4 is the most recently characterized member, which has been found 
      primarily in human cells and tissues. It interacts with SH2-containing proteins 
      such as phosphatidylinositol 3'-kinase (PI3K), Grb2, Crk-II, and CrkL. In this 
      study, we transfected IRS-4 in mouse NIH-3T3 cells that overexpress IGF-I 
      receptors. Clones expressing IRS-4 showed enhanced cellular proliferation when 
      cells were cultured in 1% fetal bovine serum without added IGF-I. Addition of 
      IGF-I enhanced cellular proliferation in cells overexpressing the IGF-I receptor 
      alone but had an even greater proliferative effect in cells overexpressing both 
      the IGF-I receptors and IRS-4. When etoposide and methylmethane sulfonate (MMS), 
      both DNA damaging agents, were added to the cells, they uniformly induced cell 
      cycle arrest. Fluorescence-activated cell sorter analysis demonstrated that the 
      arrest of the cell cycle occurred at the G(1) checkpoint, and furthermore no 
      significant degree of apoptosis was demonstrated with the use of either agent. In 
      cells, overexpressing IGF-I receptors alone, IGF-I addition enhanced cellular 
      proliferation, even in the presence of etoposide and MMS. In cells overexpressing 
      IGF-I receptors and IRS-4, the effect of IGF-I in overcoming the cell cycle 
      arrest was even more pronounced. These results suggest that IRS-4 is implicated 
      in the IGF-I receptor mitogenic signaling pathway.
FAU - Qu, B H
AU  - Qu BH
AD  - Section on Molecular Physiology, CEB/NIDDK, National Institutes of Health, 
      Bethesda, Maryland 20892-1758, USA.
FAU - Karas, M
AU  - Karas M
FAU - Koval, A
AU  - Koval A
FAU - LeRoith, D
AU  - LeRoith D
LA  - eng
PT  - Journal Article
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Growth Inhibitors)
RN  - 0 (IRS4 protein, human)
RN  - 0 (Insulin Receptor Substrate Proteins)
RN  - 0 (Irs4 protein, mouse)
RN  - 0 (Mitogens)
RN  - 0 (Phosphoproteins)
RN  - 67763-96-6 (Insulin-Like Growth Factor I)
RN  - 6PLQ3CP4P3 (Etoposide)
RN  - AT5C31J09G (Methyl Methanesulfonate)
RN  - EC 2.7.10.1 (Receptor, IGF Type 1)
SB  - IM
MH  - 3T3 Cells
MH  - Adaptor Proteins, Signal Transducing
MH  - Animals
MH  - Cell Division/*physiology
MH  - Etoposide/pharmacology
MH  - Growth Inhibitors/pharmacology
MH  - Humans
MH  - Insulin Receptor Substrate Proteins
MH  - Insulin-Like Growth Factor I/*pharmacology
MH  - Methyl Methanesulfonate/pharmacology
MH  - Mice
MH  - Mitogens/pharmacology
MH  - Phosphoproteins/genetics/*metabolism
MH  - Receptor, IGF Type 1/genetics/*metabolism
MH  - Signal Transduction
EDAT- 1999/10/26 00:00
MHDA- 1999/10/26 00:01
CRDT- 1999/10/26 00:00
PHST- 1999/10/26 00:00 [pubmed]
PHST- 1999/10/26 00:01 [medline]
PHST- 1999/10/26 00:00 [entrez]
AID - S0021-9258(19)51604-0 [pii]
AID - 10.1074/jbc.274.44.31179 [doi]
PST - ppublish
SO  - J Biol Chem. 1999 Oct 29;274(44):31179-84. doi: 10.1074/jbc.274.44.31179.