PMID- 15158680
OWN - NLM
STAT- MEDLINE
DCOM- 20040719
LR  - 20220224
IS  - 0003-9861 (Print)
IS  - 0003-9861 (Linking)
VI  - 426
IP  - 2
DP  - 2004 Jun 15
TI  - Recognition by TNF-alpha of the GPI-anchor glycan induces apoptosis of U937 
      cells.
PG  - 298-305
AB  - Tumor necrosis factor-alpha (TNF-alpha) binds to TNF-alpha receptors (TNFR) to 
      produce a hexameric (TNF-alpha)(3)-(TNFR)(3) structure that stimulates apoptosis. 
      We found by using ELISA that TNF-alpha binds to the glycosylphosphatidylinositol 
      (GPI) anchor glycans of carcinoembryonic antigen, human placental alkaline 
      phosphatase (hAP), and Tamm-Horsfall glycoprotein. These binding abilities were 
      inhibited by 10(-6)M mannose-6-phosphate. Treatment of hAP with mild acid and 
      phosphatase, which releases the N-acetylglucosamine (GlcNAc) beta1 
      -->phosphate-->6 residue from the GPI-anchor glycan of hAP, abrogated the binding 
      of TNF-alpha to hAP. Thus, TNF-alpha binds to the GlcNAcbeta1-->phosphate-->6Man 
      residue in GPI-anchor glycans. To investigate whether the carbohydrate-binding 
      ability of TNF-alpha is related to its physiological functions, human lymphoma 
      U937 cells were used. TNF-alpha stimulates U937 cell apoptosis in a 
      dose-dependent manner and the presence of mannose-6-phosphate inhibited this. 
      TNF-alpha-dependent tyrosine phosphorylation of several proteins in U937 cells 
      was also diminished by mannose-6-phosphate. Phosphatidylinositol-specific 
      phospholipase C-pretreatment also inhibited this tyrosine phosphorylation. These 
      data suggest that TNF-alpha stimulates U937 cell apoptosis by forming a 
      high-affinity nanomeric (TNF-alpha)(3)-(TNFR)(3)-(GPI-anchored glycan)(3) 
      complex. The GPI-anchored glycoprotein involved remains to be identified.
FAU - Fukushima, Keiko
AU  - Fukushima K
AD  - Department of Biochemistry, Sasaki Institute, 2-2 Kanda-Surugadai, Chiyoda-ku, 
      Tokyo 101-0062, Japan.
FAU - Ishiyama, Chikako
AU  - Ishiyama C
FAU - Yamashita, Katsuko
AU  - Yamashita K
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Arch Biochem Biophys
JT  - Archives of biochemistry and biophysics
JID - 0372430
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (GML protein, human)
RN  - 0 (GPI-Linked Proteins)
RN  - 0 (Mannosephosphates)
RN  - 0 (Membrane Proteins)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 3672-15-9 (mannose-6-phosphate)
SB  - IM
MH  - Apoptosis/drug effects/*physiology
MH  - Cell Cycle Proteins/*metabolism
MH  - Dose-Response Relationship, Drug
MH  - GPI-Linked Proteins
MH  - Humans
MH  - Mannosephosphates/*metabolism/pharmacology
MH  - Membrane Proteins/*metabolism
MH  - Neoplasm Proteins/*metabolism
MH  - Protein Binding
MH  - Signal Transduction/drug effects/*physiology
MH  - Tumor Necrosis Factor-alpha/*metabolism/pharmacology
MH  - U937 Cells
EDAT- 2004/05/26 05:00
MHDA- 2004/07/20 05:00
CRDT- 2004/05/26 05:00
PHST- 2003/12/04 00:00 [received]
PHST- 2004/02/18 00:00 [revised]
PHST- 2004/05/26 05:00 [pubmed]
PHST- 2004/07/20 05:00 [medline]
PHST- 2004/05/26 05:00 [entrez]
AID - S000398610400116X [pii]
AID - 10.1016/j.abb.2004.02.028 [doi]
PST - ppublish
SO  - Arch Biochem Biophys. 2004 Jun 15;426(2):298-305. doi: 10.1016/j.abb.2004.02.028.