| First Author | Fiala GJ | Year | 2015 |
| Journal | J Exp Med | Volume | 212 |
| Issue | 10 | Pages | 1693-708 |
| PubMed ID | 26324445 | Mgi Jnum | J:332789 |
| Mgi Id | MGI:6204001 | Doi | 10.1084/jem.20141271 |
| Citation | Fiala GJ, et al. (2015) Kidins220/ARMS binds to the B cell antigen receptor and regulates B cell development and activation. J Exp Med 212(10):1693-708 |
| abstractText | B cell antigen receptor (BCR) signaling is critical for B cell development and activation. Using mass spectrometry, we identified a protein kinase D-interacting substrate of 220 kD (Kidins220)/ankyrin repeat-rich membrane-spanning protein (ARMS) as a novel interaction partner of resting and stimulated BCR. Upon BCR stimulation, the interaction increases in a Src kinase-independent manner. By knocking down Kidins220 in a B cell line and generating a conditional B cell-specific Kidins220 knockout (B-KO) mouse strain, we show that Kidins220 couples the BCR to PLCgamma2, Ca(2+), and extracellular signal-regulated kinase (Erk) signaling. Consequently, BCR-mediated B cell activation was reduced in vitro and in vivo upon Kidins220 deletion. Furthermore, B cell development was impaired at stages where pre-BCR or BCR signaling is required. Most strikingly, lambda light chain-positive B cells were reduced sixfold in the B-KO mice, genetically placing Kidins220 in the PLCgamma2 pathway. Thus, our data indicate that Kidins220 positively regulates pre-BCR and BCR functioning. |
