PMID- 10205166
OWN - NLM
STAT- MEDLINE
DCOM- 19990611
LR  - 20181113
IS  - 0261-4189 (Print)
IS  - 0261-4189 (Linking)
VI  - 18
IP  - 8
DP  - 1999 Apr 15
TI  - A casein kinase I motif present in the cytoplasmic domain of members of the
      tumour necrosis factor ligand family is implicated in 'reverse signalling'.
PG  - 2119-26
AB  - We have identified a putative signalling feature of the cytoplasmic domains of
      the tumour necrosis factor (TNF) family members based on available amino acid
      sequence data. A casein kinase I (CKI) consensus sequence is conserved in the
      cytoplasmic domain of six of 15 members of the type II integral membrane TNF
      ligand family. We examined the phosphorylation state of transmembrane tumour
      necrosis factor-alpha (mTNF) with [32P]orthophosphate labelling and in vitro
      kinase assays, in lipopolysaccharide-stimulated RAW264.7 cells. A dimeric form of
      the type I soluble TNF receptor (sTNFR) was found to dephosphorylate mTNF. This
      effect could be prevented by treatment with phosphatase inhibitors. Recombinant
      CKI was able to phosphorylate mTNF that had been dephosphorylated by sTNFR
      ligation in vivo, and this was less effective if phosphatase inhibitors had been 
      used to prevent mTNF dephosphorylation. A mutated form of mTNF, lacking the CKI
      recognition site, cannot be phosphorylated by the enzyme. Binding of sTNFR to
      mTNF induced an increase in intracellular calcium levels in RAW264.7 cells,
      implying the presence of an associated signalling pathway. We predict that this
      CKI motif is phosphorylated in other TNF ligand members, and that it represents a
      new insight into the mechanism of 'reverse signalling' in this cytokine family.
FAU - Watts, A D
AU  - Watts AD
AD  - Departments of Pathology, University of Sydney, NSW 2006, Australia.
FAU - Hunt, N H
AU  - Hunt NH
FAU - Wanigasekara, Y
AU  - Wanigasekara Y
FAU - Bloomfield, G
AU  - Bloomfield G
FAU - Wallach, D
AU  - Wallach D
FAU - Roufogalis, B D
AU  - Roufogalis BD
FAU - Chaudhri, G
AU  - Chaudhri G
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - EMBO J
JT  - The EMBO journal
JID - 8208664
RN  - 0 (DNA Primers)
RN  - 0 (Ligands)
RN  - 0 (Receptors, Tumor Necrosis Factor)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.11.1 (Casein Kinases)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Base Sequence
MH  - Casein Kinases
MH  - Cell Membrane/metabolism
MH  - Cytoplasm/*enzymology
MH  - DNA Primers
MH  - Humans
MH  - Ligands
MH  - Molecular Sequence Data
MH  - Phosphorylation
MH  - Protein Kinases/chemistry/*metabolism
MH  - Receptors, Tumor Necrosis Factor/metabolism
MH  - Recombinant Proteins/chemistry/metabolism
MH  - Sequence Homology, Amino Acid
MH  - *Signal Transduction
MH  - Tumor Necrosis Factor-alpha/*metabolism
PMC - PMC1171296
EDAT- 1999/04/16 00:00
MHDA- 1999/04/16 00:01
CRDT- 1999/04/16 00:00
PHST- 1999/04/16 00:00 [pubmed]
PHST- 1999/04/16 00:01 [medline]
PHST- 1999/04/16 00:00 [entrez]
AID - 10.1093/emboj/18.8.2119 [doi]
PST - ppublish
SO  - EMBO J. 1999 Apr 15;18(8):2119-26. doi: 10.1093/emboj/18.8.2119.