PMID- 10201993
OWN - NLM
STAT- MEDLINE
DCOM- 19990506
LR  - 20101118
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 162
IP  - 8
DP  - 1999 Apr 15
TI  - Phosphatidylinositol 3'-kinase, but not S6-kinase, is required for insulin-like 
      growth factor-I and IL-4 to maintain expression of Bcl-2 and promote survival of 
      myeloid progenitors.
PG  - 4542-9
AB  - Phosphatidylinositol 3'-kinase (PI 3-kinase) catalyzes the formation of 3' 
      phosphoinositides and has been implicated in an intracellular signaling pathway 
      that inhibits apoptosis in both neuronal and hemopoietic cells. Here, we 
      investigated two potential downstream mediators of PI 3-kinase, the 
      serine/threonine p70 S6-kinase (S6-kinase) and the antiapoptotic protein B cell 
      lymphoma-2 (Bcl-2). Stimulation of factor-dependent cell progenitor (FDCP) cells 
      with either IL-4 or insulin-like growth factor (IGF)-I induced a 10-fold increase 
      in the activity of both PI 3-kinase and S6-kinase. Rapamycin blocked 90% of the 
      S6-kinase activity but did not affect PI 3-kinase, whereas wortmannin and 
      LY294002 inhibited the activity of both S6-kinase and PI 3-kinase. However, 
      wortmannin and LY294002, but not rapamycin, blocked the ability of IL-4 and IGF-I 
      to promote cell survival. We next established that IL-3, IL-4, and IGF-I increase 
      expression of Bcl-2 by >3-fold. Pretreatment with inhibitors of PI 3-kinase, but 
      not rapamycin, abrogated expression of Bcl-2 caused by IL-4 and IGF-I, but not by 
      IL-3. None of the cytokines affected expression of the proapoptotic protein Bax, 
      suggesting that all three cytokines were specific for Bcl-2. These data establish 
      that inhibition of PI 3-kinase, but not S6-kinase, blocks the ability of IL-4 and 
      IGF-I to increase expression of Bcl-2 and protect promyeloid cells from 
      apoptosis. The requirement for PI 3-kinase to maintain Bcl-2 expression depends 
      upon the ligand that activates the cell survival pathway.
FAU - Minshall, C
AU  - Minshall C
AD  - Laboratory of Immunophysiology, Department of Animal Sciences, College of 
      Medicine, Department of Pathology, University of Illinois, Urbana 61801, USA.
FAU - Arkins, S
AU  - Arkins S
FAU - Dantzer, R
AU  - Dantzer R
FAU - Freund, G G
AU  - Freund GG
FAU - Kelley, K W
AU  - Kelley KW
LA  - eng
GR  - AG-06246/AG/NIA NIH HHS/United States
GR  - DK-49311/DK/NIDDK NIH HHS/United States
GR  - MH-51569/MH/NIMH NIH HHS/United States
GR  - etc.
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 Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (Bax protein, mouse)
RN  - 0 (Interleukin-3)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Proto-Oncogene Proteins c-bcl-2)
RN  - 0 (bcl-2-Associated X Protein)
RN  - 207137-56-2 (Interleukin-4)
RN  - 67763-96-6 (Insulin-Like Growth Factor I)
RN  - 82115-62-6 (Interferon-gamma)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.11.1 (Ribosomal Protein S6 Kinases)
SB  - IM
MH  - Animals
MH  - Cell Line
MH  - Cell Survival/immunology
MH  - Enzyme Activation/immunology
MH  - Hematopoietic Stem Cells/cytology/*enzymology/immunology/metabolism
MH  - Insulin-Like Growth Factor I/*physiology
MH  - Interferon-gamma/pharmacology
MH  - Interleukin-3/deficiency/physiology
MH  - Interleukin-4/*physiology
MH  - Mice
MH  - Phosphatidylinositol 3-Kinases/*physiology
MH  - Proto-Oncogene Proteins/biosynthesis
MH  - Proto-Oncogene Proteins c-bcl-2/*biosynthesis
MH  - Ribosomal Protein S6 Kinases/*physiology
MH  - Signal Transduction/immunology
MH  - bcl-2-Associated X Protein
EDAT- 1999/04/14 00:00
MHDA- 1999/04/14 00:01
CRDT- 1999/04/14 00:00
PHST- 1999/04/14 00:00 [pubmed]
PHST- 1999/04/14 00:01 [medline]
PHST- 1999/04/14 00:00 [entrez]
PST - ppublish
SO  - J Immunol. 1999 Apr 15;162(8):4542-9.