| First Author | Sohn HW | Year | 2003 |
| Journal | J Exp Med | Volume | 197 |
| Issue | 11 | Pages | 1511-24 |
| PubMed ID | 12771181 | Mgi Jnum | J:120692 |
| Mgi Id | MGI:3707657 | Doi | 10.1084/jem.20021686 |
| Citation | Sohn HW, et al. (2003) Cbl-b negatively regulates B cell antigen receptor signaling in mature B cells through ubiquitination of the tyrosine kinase Syk. J Exp Med 197(11):1511-24 |
| abstractText | Members of the Cbl family of molecular adaptors play key roles in regulating tyrosine kinase-dependent signaling in a variety of cellular systems. Here we provide evidence that in B cells Cbl-b functions as a negative regulator of B cell antigen receptor (BCR) signaling during the normal course of a response. In B cells from Cbl-b-deficient mice cross-linking the BCRs resulted in sustained phosphorylation of Igalpha, Syk, and phospholipase C (PLC)-gamma2, leading to prolonged Ca2+ mobilization, and increases in extracellular signal-regulated kinase (ERK) and c-Jun NH2-terminal protein kinase (JNK) phosphorylation and surface expression of the activation marker, CD69. Image analysis following BCR cross-linking showed sustained polarization of the BCRs into large signaling-active caps associated with phosphorylated Syk in Cbl-b-deficient B cells in contrast to the BCRs in Cbl-b-expressing B cells that rapidly proceeded to form small, condensed, signaling inactive caps. Significantly, prolonged phosphorylation of Syk correlated with reduced ubiquitination of Syk indicating that Cbl-b negatively regulates BCR signaling by targeting Syk for ubiquitination. |
