Serine/threonine kinase activity associated with the cytoplasmic domain of the lymphotoxin-beta receptor in HepG2 cells.
The lymphotoxin-beta receptor (LT-betaR) has been shown to be the receptor for the membrane-bound lymphotoxin heterotrimers LTalpha1/beta2 and LTalpha2/beta1. The extracellular domain of LT-betaR shows extensive similarity with members of the tumor necrosis factor receptor family, while its cytoplasmic domain is distinct and lacks any inherent enzymatic activity. This suggests that the interaction of LT-betaR with other molecules might be important for signal transduction. Here we demonstrate the association of a fusion protein, comprising glutathione S-transferase and the cytoplasmic domain of LT-betaR (GST-LT-betaR(CD)), with several proteins in the size range 29-80 kDa from HepG2 cell lysates. We present evidence that two of these proteins are serine/threonine kinases, which associate with amino acids 324-377 of the cytoplasmic domain of LT-betaR and phosphorylate this receptor. The characteristics of these novel kinases indicate that they are distinct from the previously described tumor necrosis factor receptor-associated kinases. This suggests the presence of novel signal transduction pathway(s) for LT-betaR.
Wu
M Y
MY
Department of Microbiology and Immunology, National Yang-Ming University School of Medicine, Taipei 11221, Taiwan.
Hsu
T L
TL
Lin
W W
WW
Campbell
R D
RD
Hsieh
S L
SL
D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D001665:Binding Sites; D003593:Cytoplasm / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D053259:Lymphotoxin beta Receptor; D010449:Peptide Mapping; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism*; D047888:Receptors, Tumor Necrosis Factor, Type I; D015398:Signal Transduction; D013379:Substrate Specificity; D014407:Tumor Cells, Cultured
D000596:Amino Acids; D015703:Antigens, CD; C505697:LTBR protein, human; D053259:Lymphotoxin beta Receptor; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D011494:Protein Kinases; C094313:p60 tumor necrosis factor receptor-associated kinase; C105541:p80TRAK protein; D017346:Protein Serine-Threonine Kinases; D005978:Glutathione