PMID- 9002952
OWN - NLM
STAT- MEDLINE
DCOM- 19970224
LR  - 20210216
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 89
IP  - 2
DP  - 1997 Jan 15
TI  - Induction of hypoxia-inducible factor-1, erythropoietin, vascular endothelial 
      growth factor, and glucose transporter-1 by hypoxia: evidence against a 
      regulatory role for Src kinase.
PG  - 503-9
AB  - The induction by hypoxia of genes such as erythropoietin, vascular endothelial 
      growth factor (VEGF), and glucose transporter-1 (Glut-1) is mediated in part by a 
      transcriptional complex termed hypoxia-inducible factor-1 (HIF-1). Several lines 
      of evidence have implicated protein phosphorylation in the mechanism of 
      activation of HIF-1 by hypoxia. Recent reports have described the activation of 
      the tyrosine kinase src by severe hypoxia, and a role in the induction of VEGF by 
      severe hypoxia has been proposed. This led us to examine whether src and related 
      kinases operated more widely in the hypoxic induction of HIF-1 and 
      HIF-1-dependent genes regulated by hypoxia. Measurements of src kinase activity 
      in cells exposed to varying severities of hypoxia showed activation by severe 
      hypoxia (0.1% oxygen or catalyst induced anoxia), but not 1% oxygen. This 
      contrasted with the marked induction of HIF-1 by exposure to 1% oxygen. 
      Manipulations of src activity were produced by transient and stable transfection 
      of Hep3B cells. Despite substantial changes in src activity, no alteration was 
      seen in the normoxic or hypoxic expression of erythropoietin, VEGF, or Glut-1, or 
      in the regulation of HIF-1-dependent reporter genes inducible by hypoxia. 
      Similarly, we found that the expression of these genes in src- or c-src 
      kinase-deficient cells did not differ from wild-type cells at either 1% oxygen or 
      more severe hypoxia. These results indicate that src is not critical for the 
      hypoxic induction of HIF-1, erythropoietin, VEGF, or Glut-1.
FAU - Gleadle, J M
AU  - Gleadle JM
AD  - Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, UK.
FAU - Ratcliffe, P J
AU  - Ratcliffe PJ
LA  - eng
GR  - Wellcome Trust/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Endothelial Growth Factors)
RN  - 0 (Glucose Transporter Type 1)
RN  - 0 (HIF1A protein, human)
RN  - 0 (Hif1a protein, mouse)
RN  - 0 (Hypoxia-Inducible Factor 1)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Lymphokines)
RN  - 0 (Monosaccharide Transport Proteins)
RN  - 0 (Nuclear Proteins)
RN  - 0 (SLC2A1 protein, human)
RN  - 0 (Slc2a1 protein, mouse)
RN  - 0 (Transcription Factors)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 0 (Vascular Endothelial Growth Factors)
RN  - 11096-26-7 (Erythropoietin)
RN  - EC 2.7.10.2 (src-Family Kinases)
SB  - IM
MH  - Animals
MH  - Cell Hypoxia/genetics
MH  - Cell Line
MH  - DNA-Binding Proteins/biosynthesis/*genetics
MH  - Endothelial Growth Factors/biosynthesis/*genetics
MH  - Erythropoietin/biosynthesis/*genetics
MH  - *Gene Expression Regulation
MH  - Glucose Transporter Type 1
MH  - Humans
MH  - Hypoxia-Inducible Factor 1
MH  - Hypoxia-Inducible Factor 1, alpha Subunit
MH  - Lymphokines/biosynthesis/*genetics
MH  - Mice
MH  - Monosaccharide Transport Proteins/biosynthesis/*genetics
MH  - Nuclear Proteins/biosynthesis/*genetics
MH  - *Transcription Factors
MH  - Transfection
MH  - Vascular Endothelial Growth Factor A
MH  - Vascular Endothelial Growth Factors
MH  - *src-Family Kinases
EDAT- 1997/01/15 00:00
MHDA- 1997/01/15 00:01
CRDT- 1997/01/15 00:00
PHST- 1997/01/15 00:00 [pubmed]
PHST- 1997/01/15 00:01 [medline]
PHST- 1997/01/15 00:00 [entrez]
AID - S0006-4971(20)76750-9 [pii]
PST - ppublish
SO  - Blood. 1997 Jan 15;89(2):503-9.