A novel interaction between the juxtamembrane region of the p55 tumor necrosis factor receptor and phosphatidylinositol-4-phosphate 5-kinase.
Tumor necrosis factor-alpha (TNF-alpha) binding to its receptors leads to a diversity of biological responses. The actions of TNF are the result of the interaction of cytoplasmic proteins that bind directly to the intracellular domains of the two TNF receptors, p55 and p75. Here we report a novel interaction between the juxtamembrane region of the p55 TNF receptor and a newly discovered 47-kDa isoform of phosphatidylinositol-4-phosphate 5-kinase (PIP5K), a member of the enzyme family that generates the key signaling messenger, phosphatidylinositol 4,5-bisphosphate. The interaction was found to be specific for the p55 TNF receptor and was not observed with the p75 TNF receptor, the Fas antigen, or the p75 neurotrophin receptor, which are other members of the TNF receptor superfamily. In vitro experiments using recombinant fusion proteins verify the authenticity of the interaction between the p55 receptor and PIP5KIIbeta, a new isoform of PIP5K, but not the previously identified 53-kDa PIP5KIIalpha. Treatment of HeLa cells with TNF-alpha resulted in an increased PIP5K activity. These results indicate that phosphatidylinositol turnover may be linked to stimulation of the p55 TNF receptor and suggest that a subset of TNF responses may result from the direct association of PIP5KIIbeta with the p55 TNF receptor.
Castellino
A M
AM
Department of Cell Biology and Anatomy, Cornell University Medical College, New York, New York 10021, USA.
Parker
G J
GJ
Boronenkov
I V
IV
Anderson
R A
RA
Chao
M V
MV
D000595:Amino Acid Sequence; D015703:Antigens, CD / Q000378:metabolism*; D001483:Base Sequence; D018076:DNA, Complementary / Q000737:chemistry; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism*; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism*; D047888:Receptors, Tumor Necrosis Factor, Type I; D015398:Signal Transduction
D015703:Antigens, CD; D018076:DNA, Complementary; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D017853:Phosphotransferases (Alcohol Group Acceptor); C020077:1-phosphatidylinositol-4-phosphate 5-kinase