CD30 contains two binding sites with different specificities for members of the tumor necrosis factor receptor-associated factor family of signal transducing proteins.
CD30 is a member of the tumor necrosis factor (TNF) receptor family of proteins. CD30 can regulate proliferation of lymphocytes and may also play an important role in human immunodeficiency virus replication. However, little is known about CD30 signal transduction. We performed a yeast two-hybrid library screen with the cytoplasmic domain of CD30 and isolated multiple independent cDNAs encoding human tumor necrosis factor receptor-associated factor (TRAF) 1, TRAF2, and CRAF1 (TRAF3). The ability of TRAF1, TRAF2, and CRAF1 to associate with CD30 was confirmed using an in vitro coprecipitation assay, further demonstrating that the interaction was specific and direct. The TRAF-binding domain of CD30 was mapped to the COOH-terminal 36 amino acid residues, which contained two independent binding sites. CRAF1 bound only a single site, which contained the sequence PEQET, whereas TRAF1 and TRAF2 were capable of binding to either the PEQET site or an additional downstream domain. These data indicate that the TRAF protein binding pattern of CD30 differs from other TNF receptor family members and suggest that signaling specificity through TNF receptor family proteins may be achieved through differences in their abilities to bind TRAF proteins.
Gedrich
R W
RW
Gwen Knapp Center for Lupus and Immunology Research, University of Chicago, Chicago, Illinois 60637, USA.
Gilfillan
M C
MC
Duckett
C S
CS
Van Dongen
J L
JL
Thompson
C B
CB
D001483:Base Sequence; D001665:Binding Sites; D002460:Cell Line; D006801:Humans; D017730:Ki-1 Antigen / Q000737:chemistry / Q000378:metabolism*; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics; D015398:Signal Transduction; D047990:TNF Receptor-Associated Factor 1; D047992:TNF Receptor-Associated Factor 2
D017730:Ki-1 Antigen; D009838:Oligodeoxyribonucleotides; D011506:Proteins; D011994:Recombinant Proteins; D047990:TNF Receptor-Associated Factor 1; D047992:TNF Receptor-Associated Factor 2