Modulation of proximal signaling in normal and transformed B cells by transmembrane adapter Cbp/PAG

作者：Kalland Maria E; Solheim Silje A; Skanland Sigrid S; Tasken Kjetil; Berge Torunn^*

来源：Experimental Cell Research, 2012, 318(14): 1611-1619.

DOI：10.1016/j.yexcr.2012.05.014

• Adapter proteins
• B cells
• Src kinases
• Protein-protein interactions
• Signal transduction

The transmembrane protein Cbp/PAG (Csk binding protein/phospho-protein associated with glycosphingolipid-enriched microdomains) has a negative regulatory role in T cell activation as an adapter for C-terminal Src kinase, Csk. In T cells, membrane docking of Csk is promoted by binding to FynT-phosphorylated Cbp/PAG (pTyr317) to allow targeting of substrates residing in lipid rafts. Here, we investigate a potential parallel position for Cbp/PAG and the Src kinase Lyn in early B cell receptor signaling. Using normal and transformed B cells, we have compared signal profiles of BCR-triggered responses created by phospho-specific flow cytometry. In human normal B cells, our data show that reduced Cbp/PAG levels leads to enhanced and prolonged activation of proximal signaling mediators, while over-expression of the adapter in normal, EBV-transformed cells results in reduced calcium flux. Taken together, our findings support a negative regulatory function for Cbp/PAG in proximal BCR signaling in these cells.

• 出版日期2012-8-15