Anti-IgM induces up-regulation and tyrosine-phosphorylation of heterogeneous nuclear ribonucleoprotein K proteins (hnRNP K) in a Ramos B cell line.

Heterogeneous nuclear ribonucleoprotein K protein (hnRNP K) has diverse molecular partners implicated in signal transduction pathways, and is tyrosine-phosphorylated in response to growth factors and oxidative stress. Among the structurally distinct domains of hnRNP K, an SH3-binding domain (SH3BD) has been known to promote the association of SH3-containing tyrosine kinases and protooncoprotein Vav, which are involved in B cell receptor (BCR) signalling. In this study, we analyzed proteins of Ramos B cell line that are altered upon BCR activation with anti-IgM antibody, revealing that a certain hnRNP K isoform is up-regulated in response to anti-IgM treatment. We also showed that hnRNP K is tyrosine-phosphorylated after BCR ligation. HnRNP K lacking the SH3BD is shown not to interact with phosphorylated Vav, and Ramos cells stably expressing this mutant protein are less susceptible to anti-IgM-induced apoptosis, indicating that hnRNP K is coupled to BCR-mediated signalling and its SH3BD is required for proper signal propagation. Our results provide the first evidence that hnRNP K is involved in BCR signalling pathway.