LIME acts as a transmembrane adapter mediating BCR-dependent B-cell activation.
Assembly of a signaling complex around the transmembrane adapter LAT is essential for the transmission of T-cell receptor (TCR)-mediated signaling. However, a LAT-like molecule responsible for the initial activation events in B-cell receptor (BCR) signaling has not yet been identified. Here, we show that LIME is a transmembrane adaptor required for BCR-mediated B-cell activation. LIME was found to be expressed in mouse splenic B cells. Upon BCR cross-linking, LIME was tyrosine phosphorylated by Lyn and associated with Lyn, Grb2, PLC-gamma2, and PI3K. Reduction of LIME expression by the introduction of siRNA resulted in the disruption of BCR-mediated activation of MAPK, calcium flux, NF-AT, PI3K, and NF-kappaB. Taken together, these results establish that LIME is an essential transmembrane adaptor linking BCR ligation to the downstream signaling events that lead to B-cell activation.
Ahn
Eunseon
E
Division of Molecular Life Science, Ewha Womans University, 11-1, Daehyun-dong, Seodaemoon-gu, Seoul, 120-750, Korea.
Lee
Hyunsook
H
Yun
Yungdae
Y
D033942:Adaptor Proteins, Vesicular Transport / Q000276:immunology*; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D001483:Base Sequence; D017931:DNA Primers; D008213:Lymphocyte Activation; D051379:Mice; D010957:Plasmids; D034741:RNA, Small Interfering / Q000235:genetics; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology; D014162:Transfection
D033942:Adaptor Proteins, Vesicular Transport; D017931:DNA Primers; C480489:Lck-interacting protein, mouse; D034741:RNA, Small Interfering; D011948:Receptors, Antigen, T-Cell