PMID- 10588860
OWN - NLM
STAT- MEDLINE
DCOM- 20000111
LR  - 20191210
IS  - 0012-1606 (Print)
IS  - 0012-1606 (Linking)
VI  - 216
IP  - 1
DP  - 1999 Dec 1
TI  - The phosphoprotein protein PEA-15 inhibits Fas- but increases TNF-R1-mediated
      caspase-8 activity and apoptosis.
PG  - 16-28
AB  - We have characterized a phosphoprotein protein with a death effector domain that 
      has a novel bifunctional role in programmed cell death. The 15-kDa phosphoprotein
      enriched in astrocytes (PEA-15) inhibits Fas-mediated apoptosis and increases
      tumor necrosis factor receptor-1 (TNF-R1)-mediated apoptosis in the same cell
      type in a ligand-dependent manner. Phosphorylation appears to play a role in its 
      differential effects, since point mutations at one or both phosphorylation
      consensus sites within PEA-15 destroy its effect on Fas-mediated, but not
      TNF-R1-mediated, apoptosis. Furthermore, the differential effect is evident at
      the level of caspase-8 activity which is inhibited via Fas activation, but
      increased via TNF-R1 activation upon PEA-15 expression. These results show that
      PEA-15 provides a potential mechanism during development for distinguishing
      between diverse extracellular death-inducing signals that culminate either in
      apoptosis or in survival.
CI  - Copyright 1999 Academic Press.
FAU - Estelles, A
AU  - Estelles A
AD  - Department of Molecular Pharmacology, Stanford University School of Medicine,
      Stanford, California, 94305-5332, USA.
FAU - Charlton, C A
AU  - Charlton CA
FAU - Blau, H M
AU  - Blau HM
LA  - eng
GR  - AG09521/AG/NIA NIH HHS/United States
GR  - CA59717/CA/NCI NIH HHS/United States
GR  - HD18179/HD/NICHD NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Dev Biol
JT  - Developmental biology
JID - 0372762
RN  - 0 (Antibodies)
RN  - 0 (Apoptosis Regulatory Proteins)
RN  - 0 (NF-kappa B)
RN  - 0 (Pea15 protein, mouse)
RN  - 0 (Phosphoproteins)
RN  - 0 (Receptors, Tumor Necrosis Factor)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (fas Receptor)
RN  - EC 3.4.22.- (Casp8 protein, mouse)
RN  - EC 3.4.22.- (Casp9 protein, mouse)
RN  - EC 3.4.22.- (Caspase 8)
RN  - EC 3.4.22.- (Caspase 9)
RN  - EC 3.4.22.- (Caspases)
SB  - IM
MH  - 3T3 Cells
MH  - Amino Acid Sequence
MH  - Animals
MH  - Antibodies/immunology
MH  - Apoptosis/*drug effects
MH  - Apoptosis Regulatory Proteins
MH  - Caspase 8
MH  - Caspase 9
MH  - Caspases/*metabolism
MH  - Enzyme Activation/drug effects
MH  - Gene Expression
MH  - Mice
MH  - Molecular Sequence Data
MH  - Mutation
MH  - NF-kappa B/metabolism
MH  - Phosphoproteins/genetics/*pharmacology
MH  - Phosphorylation
MH  - Receptors, Tumor Necrosis Factor/*metabolism
MH  - Signal Transduction
MH  - Tumor Necrosis Factor-alpha/pharmacology
MH  - fas Receptor/immunology/*metabolism
EDAT- 1999/12/10 00:00
MHDA- 1999/12/10 00:01
CRDT- 1999/12/10 00:00
PHST- 1999/12/10 00:00 [pubmed]
PHST- 1999/12/10 00:01 [medline]
PHST- 1999/12/10 00:00 [entrez]
AID - 10.1006/dbio.1999.9510 [doi]
AID - S0012-1606(99)99510-6 [pii]
PST - ppublish
SO  - Dev Biol. 1999 Dec 1;216(1):16-28. doi: 10.1006/dbio.1999.9510.