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Published March 10, 1995 | public
Journal Article

Involvement of CRAF1, a relative of TRAF, in CD40 signaling

Abstract

CD40 is a receptor on the surface of B lymphocytes, the activation of which leads to B cell survival, growth, and differentiation. A yeast two-hybrid screen identified a gene, CRAF1, encoding a protein that interacts directly with the CD40 cytoplasmic tail through a region of similarity to the tumor necrosis factor-alpha (TNF-alpha) receptor-associated factors. Overexpression of a truncated CRAF1 gene inhibited CD40-mediated up-regulation of CD23. A region of CRAF1 was similar to the TNF-alpha receptor-associated factors TRAF1 and TRAF2 and so defined a shared TRAF-C domain that was necessary and sufficient for CD40 binding and homodimerization. The CRAF1 sequence also predicted a long amphipathic helix, a pattern of five zinc fingers, and a zinc ring finger. It is likely that other members of the TNF receptor superfamily use CRAF-related proteins in their signal transduction processes.

Additional Information

© 1995 American Association for the Advancement of Science. Received 22 November 1994; accepted 2 February 1995. We thank P. Svec and T. Hawkins for their help in sequencing and J. Jacob for critical reading of the manuscript. G.C. and Z.-Y. are recipients of an Irvington House Institute fellowship and a Leukemia Society special fellowship, respectively. S.L. is an Arthritis Investigator of the Arthritis Foundation. D.B. is an American Cancer Society Research Professor. A.M.C. is supported by the Medical Scientist Training Program grant 5-T32-GM07367. S.L., A.M.C., and D.I.H. are also supported in part by Biogen, Cambridge, MA. This work was supported by National Institute of Allergy and Infectious Diseases grant A122346 (D.B.) and by National Cancer Institute (NCI) grant R01-CA55713 to S.L.

Additional details

Created:
August 20, 2023
Modified:
October 20, 2023