PMID- 14562045
OWN - NLM
STAT- MEDLINE
DCOM- 20031126
LR  - 20091119
IS  - 0950-9232 (Print)
IS  - 0950-9232 (Linking)
VI  - 22
IP  - 46
DP  - 2003 Oct 16
TI  - An increase in the expression and total activity of endogenous p60(c-Src) in 
      several factor-independent mutants of a human GM-CSF-dependent leukemia cell line 
      (TF-1).
PG  - 7170-80
AB  - Growth factor independence of hematopoietic cells can be induced by ectopic 
      expression of a variety of oncogenes encoding receptor or cytoplasmic tyrosine 
      kinases. To examine whether the activation of tyrosine kinases occurs in 
      factor-independent mutants in vivo, the tyrosine-phosphorylated proteins from 14 
      factor-independent mutants of a GM-CSF-dependent cell line (TF-1) were analysed. 
      These mutants did not secrete any growth-stimulating activity for TF-1 cells, 
      suggesting that activation of intracellular signaling rather than an autocrine 
      stimulation by secreted growth factors is responsible for their 
      factor-independent growth. In 11 out of 14 GM-CSF-independent mutants analysed, a 
      constitutively tyrosine-phosphorylated protein of 60 kDa was detected, which was 
      subsequently identified as p60(c-Src). The kinase activity of p60(c-Src) was 
      increased up to 12-fold in these mutants, which was at least in part due to 
      overexpression of the c-src gene on the RNA and protein level. The Src substrate 
      Sam68 showed an increased phosphorylation in mutants with high Src activity, 
      suggesting that p60(c-Src) triggers downstream signaling in these cells. 
      Treatment of the factor-independent mutants with the Src kinase inhibitor PP2 
      resulted in a reduced proliferation, demonstrating that Src kinases are essential 
      for these cells for maximal proliferation. Further analysis of factor-independent 
      mutants with low or undetectable Src activity revealed a constitutive 
      phosphorylation of the common beta chain of the GM-CSF receptor and STAT5. Our 
      data indicate an increase in the expression and total activity of endogenous 
      p60(c-Src) in several GM-CSF-independent TF-1 mutants, further underlining the 
      role of Src in the process of autonomous growth of hematopoietic cells.
FAU - Horn, Stefan
AU  - Horn S
AD  - Zentrum fur Experimentelle Medizin, Institut fur Biochemie und Molekularbiologie 
      I, Zellulare Signaltransduktion, Universitatsklinikum Hamburg-Eppendorf, 
      Martinistr 52, D-20246 Hamburg, Germany.
FAU - Meyer, Johann
AU  - Meyer J
FAU - Stocking, Carol
AU  - Stocking C
FAU - Ostertag, Wolfram
AU  - Ostertag W
FAU - Jucker, Manfred
AU  - Jucker M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Oncogene
JT  - Oncogene
JID - 8711562
RN  - 0 (DNA Primers)
RN  - 83869-56-1 (Granulocyte-Macrophage Colony-Stimulating Factor)
RN  - EC 2.7.10.2 (Proto-Oncogene Proteins pp60(c-src))
SB  - IM
MH  - Base Sequence
MH  - Cell Division/drug effects
MH  - Clone Cells
MH  - DNA Primers
MH  - Gene Expression Regulation, Enzymologic/drug effects
MH  - Gene Expression Regulation, Neoplastic/*drug effects
MH  - Granulocyte-Macrophage Colony-Stimulating Factor/*pharmacology
MH  - Humans
MH  - Leukemia, Erythroblastic, Acute
MH  - Mutagenesis
MH  - Phosphorylation
MH  - Proto-Oncogene Proteins pp60(c-src)/*genetics/*metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Tumor Cells, Cultured
EDAT- 2003/10/17 05:00
MHDA- 2003/12/03 05:00
CRDT- 2003/10/17 05:00
PHST- 2003/10/17 05:00 [pubmed]
PHST- 2003/12/03 05:00 [medline]
PHST- 2003/10/17 05:00 [entrez]
AID - 1206856 [pii]
AID - 10.1038/sj.onc.1206856 [doi]
PST - ppublish
SO  - Oncogene. 2003 Oct 16;22(46):7170-80. doi: 10.1038/sj.onc.1206856.