| First Author | Numaga-Tomita T | Year | 2016 |
| Journal | Biochem J | Volume | 473 |
| Issue | 2 | Pages | 201-10 |
| PubMed ID | 26554024 | Mgi Jnum | J:237671 |
| Mgi Id | MGI:5816434 | Doi | 10.1042/BJ20150596 |
| Citation | Numaga-Tomita T, et al. (2016) TRPC3 amplifies B-cell receptor-induced ERK signalling via protein kinase D-dependent Rap1 activation. Biochem J 473(2):201-10 |
| abstractText | Sustained activation of extracellular-signal-regulated kinase (ERK) has an important role in the decision regarding the cell fate of B-lymphocytes. Recently, we demonstrated that the diacylglycerol-activated non-selective cation channel canonical transient receptor potential 3 (TRPC3) is required for the sustained ERK activation induced by the B-cell receptor. However, the signalling mechanism underlying TRPC3-mediated ERK activation remains elusive. In the present study, we have shown that TRPC3 mediates Ca(2+) influx to sustain activation of protein kinase D (PKD) in a protein kinase C-dependent manner in DT40 B-lymphocytes. The later phase of ERK activation depends on the small G-protein Rap1, known as a downstream target of PKD, whereas the earlier phase of ERK activation depends on the Ras protein. It is of interest that sustained ERK phosphorylation is required for the full induction of the immediate early gene Egr-1 (early growth response 1). These results suggest that TRPC3 reorganizes the BCR signalling complex by switching the subtype of small G-proteins to sustain ERK activation in B-lymphocytes. |
