PMID- 11278471
OWN - NLM
STAT- MEDLINE
DCOM- 20010614
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 276
IP  - 17
DP  - 2001 Apr 27
TI  - Tumor necrosis factor-alpha induction of endothelial ephrin A1 expression is 
      mediated by a p38 MAPK- and SAPK/JNK-dependent but nuclear factor-kappa 
      B-independent mechanism.
PG  - 13771-7
AB  - Tumor necrosis factor-alpha (TNF-alpha) is a multifunctional cytokine that 
      induces a broad spectrum of responses including angiogenesis. Angiogenesis 
      promoted by TNF-alpha is mediated, at least in part, by ephrin A1, a member of 
      the ligand family for Eph receptor tyrosine kinases. Although TNF-alpha induces 
      ephrin A1 expression in endothelial cells, the signaling pathways mediating 
      ephrin A1 induction remain unknown. In this study, we investigated the signaling 
      mechanisms of TNF-alpha-dependent induction of ephrin A1 in endothelial cells. 
      Both TNFR1 and TNFR2 appear to be involved in regulating ephrin A1 expression in 
      endothelial cells, because neutralizing antibodies to either TNFR1 or TNFR2 
      inhibited TNF-alpha-induced ephrin A1 expression. Inhibition of nuclear 
      factor-kappaB (NF-kappaB) activation by a trans-dominant inhibitory isoform of 
      mutant IkappaBalpha did not affect ephrin A1 induction, suggesting that NF-kappaB 
      proteins are not major regulators of ephrin A1 expression. In contrast, ephrin A1 
      induction was blocked by inhibition of p38 mitogen-activated protein kinase 
      (MAPK) or SAPK/JNK, but not p42/44 MAPK, using either selective chemical 
      inhibitors or dominant-negative forms of p38 MAPK or TNF receptor-associated 
      factor 2. These findings indicate that TNF-alpha-induced ephrin A1 expression is 
      mediated through JNK and p38 MAPK signaling pathways. Taken together, the results 
      of our study demonstrated that induction of ephrin A1 in endothelial cells by 
      TNF-alpha is mediated through both p38 MAPK and SAPK/JNK, but not p42/44 MAPK or 
      NF-kappaB, pathways.
FAU - Cheng, N
AU  - Cheng N
AD  - Department of Cell Biology, Vanderbilt University Medical School, Nashville, 
      Tennessee 37232, USA.
FAU - Chen, J
AU  - Chen J
LA  - eng
GR  - R01 HD36400/HD/NICHD NIH HHS/United States
GR  - T-32 CA09592/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20010202
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Antigens, CD)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Ephrin-A1)
RN  - 0 (Flavonoids)
RN  - 0 (Ligands)
RN  - 0 (NF-kappa B)
RN  - 0 (Protein Isoforms)
RN  - 0 (Receptors, Tumor Necrosis Factor)
RN  - 0 (Receptors, Tumor Necrosis Factor, Type I)
RN  - 0 (Receptors, Tumor Necrosis Factor, Type II)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 2.7.- (Phosphotransferases)
RN  - EC 2.7.1.24 (Mitogen-Activated Protein Kinase 9)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
RN  - SJE1IO5E3I (2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one)
SB  - IM
MH  - Adenoviridae/genetics
MH  - Antigens, CD/metabolism
MH  - Blotting, Northern
MH  - Blotting, Western
MH  - Cells, Cultured
MH  - Dose-Response Relationship, Drug
MH  - Electrophoresis, Polyacrylamide Gel
MH  - Endothelium, Vascular/cytology/*metabolism
MH  - Enzyme Activation
MH  - Enzyme Inhibitors/pharmacology
MH  - Ephrin-A1
MH  - Flavonoids/pharmacology
MH  - *Gene Expression Regulation, Enzymologic
MH  - Genes, Dominant
MH  - Humans
MH  - Kinetics
MH  - Ligands
MH  - Mitogen-Activated Protein Kinase 9
MH  - Mitogen-Activated Protein Kinases/*metabolism
MH  - Models, Biological
MH  - NF-kappa B/antagonists & inhibitors/*metabolism
MH  - Phosphotransferases/metabolism
MH  - *Protein Biosynthesis
MH  - Protein Isoforms
MH  - Receptors, Tumor Necrosis Factor/metabolism
MH  - Receptors, Tumor Necrosis Factor, Type I
MH  - Receptors, Tumor Necrosis Factor, Type II
MH  - Signal Transduction
MH  - Time Factors
MH  - Tumor Necrosis Factor-alpha/genetics/*metabolism
MH  - Umbilical Cord/cytology
MH  - *Up-Regulation
MH  - p38 Mitogen-Activated Protein Kinases
EDAT- 2001/03/30 10:00
MHDA- 2001/06/15 10:01
CRDT- 2001/03/30 10:00
PHST- 2001/03/30 10:00 [pubmed]
PHST- 2001/06/15 10:01 [medline]
PHST- 2001/03/30 10:00 [entrez]
AID - S0021-9258(20)78820-4 [pii]
AID - 10.1074/jbc.M009147200 [doi]
PST - ppublish
SO  - J Biol Chem. 2001 Apr 27;276(17):13771-7. doi: 10.1074/jbc.M009147200. Epub 2001 
      Feb 2.