PMID- 11078718
OWN - NLM
STAT- MEDLINE
DCOM- 20010104
LR  - 20200930
IS  - 0363-6143 (Print)
IS  - 0363-6143 (Linking)
VI  - 279
IP  - 6
DP  - 2000 Dec
TI  - Serine phosphorylation of p60 tumor necrosis factor receptor by PKC-delta in 
      TNF-alpha-activated neutrophils.
PG  - C2011-8
AB  - Tumor necrosis factor-alpha (TNF-alpha) triggers degranulation and oxygen radical 
      release in adherent neutrophils. The p60TNF receptor (p60TNFR) is responsible for 
      proinflammatory signaling, and protein kinase C (PKC) is a candidate for the 
      regulation of p60TNFR. Both TNF-alpha and the PKC-activator phorbol 12-myristate 
      13-acetate triggered phosphorylation of p60TNFR. Receptor phosphorylation was on 
      both serine and threonine but not on tyrosine residues. The PKC-delta isotype is 
      a candidate enzyme for serine phosphorylation of p60TNFR. Staurosporine and the 
      PKC-delta inhibitor rottlerin inhibited TNF-alpha-triggered serine but not 
      threonine phosphorylation. Serine phosphorylation was associated with receptor 
      desensitization, as inhibition of PKC resulted in enhanced degranulation 
      (elastase release). After neutrophil activation, PKC-delta was the only PKC 
      isotype that associated with p60TNFR within the correct time frame for receptor 
      phosphorylation. In vitro, only PKC-delta, but not the alpha-, betaI-, betaII-, 
      or zeta-isotypes, was competent to phosphorylate the receptor, indicating that 
      p60TNFR is a direct substrate for PKC-delta. These findings suggest a selective 
      role for PKC-delta in negative regulation of the p60TNFR and of TNF-alpha-induced 
      signaling.
FAU - Kilpatrick, L E
AU  - Kilpatrick LE
AD  - Departments of Pediatrics and Biochemistry/Biophysics, University of Pennsylvania 
      School of Medicine, and the Joseph Stokes Jr. Research Institute of the 
      Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA. 
      kilpatrick@email.chop.edu
FAU - Song, Y H
AU  - Song YH
FAU - Rossi, M W
AU  - Rossi MW
FAU - Korchak, H M
AU  - Korchak HM
LA  - eng
GR  - AI-24840/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Am J Physiol Cell Physiol
JT  - American journal of physiology. Cell physiology
JID - 100901225
RN  - 0 (Acetophenones)
RN  - 0 (Benzopyrans)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Isoenzymes)
RN  - 0 (Receptors, Tumor Necrosis Factor)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 452VLY9402 (Serine)
RN  - E29LP3ZMUH (rottlerin)
RN  - EC 2.7.11.13 (PRKCD protein, human)
RN  - EC 2.7.11.13 (Protein Kinase C)
RN  - EC 2.7.11.13 (Protein Kinase C-delta)
RN  - EC 3.4.21.36 (Pancreatic Elastase)
RN  - H88EPA0A3N (Staurosporine)
SB  - IM
MH  - Acetophenones/pharmacology
MH  - Benzopyrans/pharmacology
MH  - Down-Regulation/immunology
MH  - Enzyme Inhibitors/pharmacology
MH  - Humans
MH  - Isoenzymes/antagonists & inhibitors/*metabolism
MH  - Neutrophil Activation/drug effects/*immunology
MH  - Neutrophils/drug effects/*enzymology/immunology
MH  - Pancreatic Elastase/metabolism
MH  - Phosphorylation
MH  - Protein Kinase C/antagonists & inhibitors/*metabolism
MH  - Protein Kinase C-delta
MH  - Receptors, Tumor Necrosis Factor/*metabolism
MH  - Serine/metabolism
MH  - Signal Transduction/drug effects/immunology
MH  - Staurosporine/pharmacology
MH  - Tumor Necrosis Factor-alpha/*pharmacology
EDAT- 2000/11/18 11:00
MHDA- 2001/02/28 10:01
CRDT- 2000/11/18 11:00
PHST- 2000/11/18 11:00 [pubmed]
PHST- 2001/02/28 10:01 [medline]
PHST- 2000/11/18 11:00 [entrez]
AID - 10.1152/ajpcell.2000.279.6.C2011 [doi]
PST - ppublish
SO  - Am J Physiol Cell Physiol. 2000 Dec;279(6):C2011-8. doi: 
      10.1152/ajpcell.2000.279.6.C2011.