| First Author | Wang HM | Year | 2015 |
| Journal | J Biol Chem | Volume | 290 |
| Issue | 9 | Pages | 5256-66 |
| PubMed ID | 25586186 | Mgi Jnum | J:219331 |
| Mgi Id | MGI:5620529 | Doi | 10.1074/jbc.M114.618496 |
| Citation | Wang HM, et al. (2015) Scaffold Protein JLP Is Critical for CD40 Signaling in B Lymphocytes. J Biol Chem 290(9):5256-66 |
| abstractText | CD40 expression on the surface of B lymphocytes is essential for their biological function and fate decision. The engagement of CD40 with its cognate ligand, CD154, leads to a sequence of cellular events in B lymphocytes, including CD40 cytoplasmic translocation, a temporal and spatial organization of effector molecules, and a cascade of CD40-induced signal transduction. The JLP scaffold protein was expressed in murine B lymphocytes. Using B lymphocytes from jlp-deficient mice, we observed that JLP deficiency resulted in defective CD40 internalization upon CD154/CD40 engagement. Examination of interactions and co-localization among CD40, JLP, dynein, and Rab5 in B lymphocytes suggested that CD40 internalization is a process of JLP-mediated vesicle transportation that depends on Rab5 and dynein. JLP deficiency also diminished CD40-dependent activation of MAPK and JNK, but not NF-kappaB. Inhibiting vesicle transportation from the direction of cell periphery to the cell center by a dynein inhibitor (ciliobrevin D) impaired both CD154-induced CD40 internalization and CD40-dependent MAPK activities in B lymphocytes. Collectively, our data demonstrate a novel role of the JLP scaffold protein in the bridging of CD154-triggered CD40 internalization and CD40-dependent signaling in splenic B lymphocytes. |
