Modulation of proximal signaling in normal and transformed B cells by transmembrane adapter Cbp/PAG.
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.
The Biotechnology Centre of Oslo, Nordic EMBL Partnership, University of Oslo, P.O. Box 1125 Blindern, N-0317 Oslo, Norway.
Maria E
ME
Kalland
Silje A
SA
Solheim
Sigrid S
SS
Skånland
Kjetil
K
Taskén
Torunn
T
Berge
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D001402:B-Lymphocytes / Q000166:cytology* / Q000378:metabolism* / Q000473:pathology; D002460:Cell Line; D002461:Cell Line, Transformed; D005434:Flow Cytometry; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism; D015398:Signal Transduction
D048868:Adaptor Proteins, Signal Transducing; D008565:Membrane Proteins; C498710:PAG1 protein, human; D011947:Receptors, Antigen, B-Cell