Depletion of hsp90beta induces multiple defects in B cell receptor signaling.
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. Hsp90beta-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 Hsp90beta-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 Hsp90beta gene efficiently restores all of the defects. Unexpectedly, however, introducing the Hsp90alpha 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 Hsp90beta-specific function.
Shinozaki
Fumika
F
Department of Biophysics and Biochemistry, and Undergraduate Program for Bioinformatics and Systems Biology, Graduate School of Science, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan.
Minami
Michiko
M
Chiba
Tomoki
T
Suzuki
Miho
M
Yoshimatsu
Katsuhiko
K
Ichikawa
Yoshimasa
Y
Terasawa
Kazuya
K
Emori
Yasufumi
Y
Matsumoto
Ken
K
Kurosaki
Tomohiro
T
Nakai
Akira
A
Tanaka
Keiji
K
Minami
Yasufumi
Y
D000818:Animals; D002460:Cell Line; D002645:Chickens; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005786:Gene Expression Regulation; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism*; D006358:Hot Temperature; D010957:Plasmids / Q000378:metabolism; D040901:Proteomics / Q000379:methods; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism*; D015398:Signal Transduction; D014162:Transfection
D018841:HSP90 Heat-Shock Proteins; D011947:Receptors, Antigen, B-Cell; D048049:Extracellular Signal-Regulated MAP Kinases