PMID- 10469654
OWN - NLM
STAT- MEDLINE
DCOM- 19991028
LR  - 20211203
IS  - 0261-4189 (Print)
IS  - 0261-4189 (Linking)
VI  - 18
IP  - 17
DP  - 1999 Sep 1
TI  - STAT5 as a molecular regulator of proliferation, differentiation and apoptosis in
      hematopoietic cells.
PG  - 4754-65
AB  - Signal transducers and activators of transcription (STATs) play key roles in
      growth factor-mediated intracellular signal transduction. In the present study
      using a constitutively active STAT5 mutant, we show that STAT5 has pleiotropic
      functions regulating cell proliferation, differentiation and apoptosis in an
      IL-3-dependent Ba/F3 cell line. The mutant STAT5 possessed constitutive tyrosine 
      phosphorylation and DNA binding activity, induced expression of bcl-xL and pim-1 
      in the absence of IL-3 in Ba/F3 cells, and rendered Ba/F3 cells
      factor-independent. Unexpectedly, IL-3 treatment of the factor-independent Ba/F3 
      cells expressing the constitutively active STAT5 resulted in apoptosis within 24 
      h, or differentiation followed by cell death. In these cells, mRNA expression of 
      growth inhibitory genes downstream of STAT5 such as CIS, JAB/SOCS-1/SSI-1, and
      p21(WAF1/Cip1) was highly induced, correlating with prolonged
      hyper-phosphorylation of the mutant STAT5 after IL-3 stimulation. Of the
      STAT5-regulated genes, we found that constitutive expression of JAB/SOCS-1/SSI-1 
      was sufficient to induce apoptosis of Ba/F3 cells, while p21(WAF1/Cip1) could
      induce differentiation of these cells. In contrast, constitutive expression of
      pim-1 was sufficient to induce IL-3-independent growth of Ba/F3 cells. These
      findings suggest that a single transcription factor regulates cell fate by
      varying the intensity and duration of the expression of a set of target genes.
FAU - Nosaka, T
AU  - Nosaka T
AD  - Department of Hematopoietic Factors, The Institute of Medical Science, University
      of Tokyo, Minato-ku, Tokyo 108-8639, Japan.
FAU - Kawashima, T
AU  - Kawashima T
FAU - Misawa, K
AU  - Misawa K
FAU - Ikuta, K
AU  - Ikuta K
FAU - Mui, A L
AU  - Mui AL
FAU - Kitamura, T
AU  - Kitamura T
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - EMBO J
JT  - The EMBO journal
JID - 8208664
RN  - 0 (Cdkn1a protein, mouse)
RN  - 0 (Cyclin-Dependent Kinase Inhibitor p21)
RN  - 0 (Cyclins)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Interleukin-3)
RN  - 0 (Milk Proteins)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (STAT5 Transcription Factor)
RN  - 0 (Trans-Activators)
RN  - 0 (Tumor Suppressor Protein p53)
RN  - 9007-49-2 (DNA)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.10.2 (Jak2 protein, mouse)
RN  - EC 2.7.10.2 (Janus Kinase 2)
RN  - EC 2.7.11.1 (Pim1 protein, mouse)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-pim-1)
SB  - IM
MH  - Animals
MH  - Apoptosis/*physiology
MH  - Cell Cycle/physiology
MH  - Cell Differentiation/physiology
MH  - Cell Division/physiology
MH  - Cell Line
MH  - Cyclin-Dependent Kinase Inhibitor p21
MH  - Cyclins/metabolism
MH  - DNA/analysis
MH  - DNA-Binding Proteins/*physiology
MH  - Flow Cytometry
MH  - Gene Expression Regulation, Leukemic
MH  - Interleukin-3/metabolism
MH  - Janus Kinase 2
MH  - Mice
MH  - *Milk Proteins
MH  - *Protein Serine-Threonine Kinases
MH  - Protein-Tyrosine Kinases/metabolism
MH  - Proto-Oncogene Proteins/metabolism
MH  - Proto-Oncogene Proteins c-pim-1
MH  - STAT5 Transcription Factor
MH  - Signal Transduction
MH  - Time Factors
MH  - Trans-Activators/*physiology
MH  - Transfection
MH  - Tumor Suppressor Protein p53/metabolism
MH  - Up-Regulation
PMC - PMC1171548
EDAT- 1999/09/02 00:00
MHDA- 1999/09/02 00:01
CRDT- 1999/09/02 00:00
PHST- 1999/09/02 00:00 [pubmed]
PHST- 1999/09/02 00:01 [medline]
PHST- 1999/09/02 00:00 [entrez]
AID - 10.1093/emboj/18.17.4754 [doi]
PST - ppublish
SO  - EMBO J. 1999 Sep 1;18(17):4754-65. doi: 10.1093/emboj/18.17.4754.