Cell-surface CD74 initiates a signaling cascade leading to cell proliferation and survival.
CD74 is an integral membrane protein that was thought to function mainly as an MHC class II chaperone. However, CD74 was recently shown to have a role as an accessory-signaling molecule. Our studies demonstrated that CD74 regulates B-cell differentiation by inducing a pathway leading to the activation of transcription mediated by the NF-kappaB p65/RelA homodimer and its coactivator, TAF(II)105. Here, we show that CD74 stimulation with anti-CD74 antibody leads to an induction of a signaling cascade resulting in NF-kappaB activation, entry of the stimulated cells into the S phase, elevation of DNA synthesis, cell division, and augmented expression of BCL-X(L). These studies therefore demonstrate that surface CD74 functions as a survival receptor.
Department of Immunology, Weizmann Institute of Science, Rehovot, Israel 76100.
Diana
D
Starlets
Yael
Y
Gore
Inbal
I
Binsky
Michal
M
Haran
Nurit
N
Harpaz
Lev
L
Shvidel
Shirly
S
Becker-Herman
Alain
A
Berrebi
Idit
I
Shachar
D000818:Animals; D000944:Antigens, Differentiation, B-Lymphocyte / Q000235:genetics / Q000276:immunology*; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology*; D002470:Cell Survival / Q000235:genetics / Q000276:immunology; D004247:DNA / Q000235:genetics / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology*; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D016196:S Phase / Q000276:immunology*; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D035381:TATA-Binding Protein Associated Factors / Q000235:genetics / Q000276:immunology; D051996:Transcription Factor RelA / Q000235:genetics / Q000276:immunology; D035362:Transcription Factor TFIID / Q000235:genetics / Q000276:immunology; D014158:Transcription, Genetic / Q000235:genetics / Q000276:immunology; D014407:Tumor Cells, Cultured; D051020:bcl-X Protein / Q000235:genetics / Q000276:immunology
D000944:Antigens, Differentiation, B-Lymphocyte; C494812:Bcl2l1 protein, mouse; D000949:Histocompatibility Antigens Class II; C498144:Rela protein, mouse; D035381:TATA-Binding Protein Associated Factors; C491103:Taf4b protein, mouse; D051996:Transcription Factor RelA; D035362:Transcription Factor TFIID; D051020:bcl-X Protein; C045084:invariant chain; D004247:DNA