Depletion of Hsp90β Induces Multiple Defects in B Cell Receptor Signaling

• Published in: The Journal of biological chemistry Vol. 281; no. 24; p. 16361
• Main Authors: Fumika Shinozaki, Michiko Minami, Tomoki Chiba, Miho Suzuki, Katsuhiko Yoshimatsu, Yoshimasa Ichikawa, Kazuya Terasawa, Yasufumi Emori, Ken Matsumoto, Tomohiro Kurosaki, Akira Nakai, Keiji Tanaka, Yasufumi Minami
• Format: Journal Article
• Language: English
• Published: American Society for Biochemistry and Molecular Biology 16.06.2006
• DOI: 10.1074/jbc.M600891200
• ISSN: 0021-9258

Hsp90 participates in many distinct aspects of cellular functions and accomplishes these roles by interacting with multiple client proteins. To gain insight into the interactions between Hsp90 and its clients, here we have reduced the protein level of Hsp90 in avian cells by gene targeting in an attempt to elicit the otherwise undetectable (because of the vast amount of cellular Hsp90) Hsp90-interacting proteins. Hsp90β-deficient cells can grow, albeit more slowly than wild-type cells. B cell antigen receptor signaling is multiply impaired in these mutant cells; in particular, the amount of immunoglobulin M heavy chain protein is markedly reduced. Furthermore, serum activation does not promote ERK phosphorylation in Hsp90β-deficient cells. These multifaceted depressive effects seem to be provoked independently of each other and possibly recapitulate the proteome-wide in vivo functions of Hsp90. Reintroduction of the Hsp90β gene efficiently restores all of the defects. Unexpectedly, however, introducing the Hsp90α gene is also effective in restoration; thus, these defects might be caused by a reduction in the total expression of Hsp90 rather than by loss of Hsp90β-specific function.