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XB-ART-3233
J Biol Chem. September 10, 2004; 279 (37): Sef interacts with TAK1 and mediates JNK activation and apoptosis.
Yang X
,
Kovalenko D
,
Nadeau RJ
,
Harkins LK
,
Mitchell J
,
Zubanova O
,
Chen PY
,
Friesel R
.
Abstract Sef was recently identified as a negative regulator of fibroblast growth factor (FGF) signaling in a genetic screen of zebrafish and subsequently in mouse and humans. By inhibiting FGFR1 tyrosine phosphorylation and/or Ras downstream events, Sef inhibits FGF-mediated ERK activation and cell proliferation as well as PC12 cell differentiation. Here we show that Sef and a deletion mutant of Sef lacking the extracellular domain (SefIC) physically interact with TAK1 (transforming growth factor-beta-associated kinase) and activate JNK through a TAK1-MKK4-JNK pathway. Sef and SefIC overexpression also resulted in apoptotic cell death, while dominant negative forms of MKK4 and TAK1 blocked Sef-mediated JNK activation and attendant 293T cell apoptosis. These investigations reveal a novel activating function of Sef that is distinct from its inhibitory effect on FGF receptor signaling and ERK activation.Pubmed Id: 15277532 Article link: J Biol Chem.Grant support:
DE13248 NIDCR NIH HHS, HL65301 NHLBI NIH HHS , RR15555 NCRR NIH HHS Genes referenced: fgfr1 map3k7 mapk1 mapk8 nr2c2 tfcp2 Antibodies referenced: |
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