Protein tyrosine kinases p53/56lyn and p72syk in MHC class I-mediated signal transduction in B lymphoma cells.

TY - JOUR

T1 - Protein tyrosine kinases p53/56lyn and p72syk in MHC class I-mediated signal transduction in B lymphoma cells.

AU - Pedersen, Anders Elm

AU - Bregenholt, S

AU - Skov, S

AU - Vrang, M L

AU - Claesson, M H

N1 - Keywords: Animals; Calcium; Chickens; Cross-Linking Reagents; Enzyme Precursors; Histocompatibility Antigens Class I; Humans; Intracellular Signaling Peptides and Proteins; Lymphoma, B-Cell; Phosphorylation; Protein-Tyrosine Kinases; Signal Transduction; Tumor Cells, Cultured; src-Family Kinases

PY - 1998

Y1 - 1998

N2 - Crosslinking of major histocompatibility complex class I (MHC-I) molecules on the surface of human B lymphoma cells was shown to induce protein tyrosine phosphorylation and mobilization of intracellular free calcium. Immunoprecipitations indicated that the protein tyrosine kinases p53/56lyn and p72syk are among the tyrosine-phosphorylated proteins. The kinetics of phosphorylation of these kinases after MHC-I crosslinking differ from the kinetics observed after crosslinking of the B cell antigen receptor (BCR). Additional experiments were performed with chicken lyn- and syk-negative DT40 B cells and the results indicate that these two kinases have different substrate specificity and regulate intracellular free calcium differently in response to MHC-I crosslinking. In addition MHC-I crosslinking of a sIgM-negative DT40 chicken B cell variant results in less activity of tyrosine kinases and less mobilization of intracellular free calcium compared with MHC-I crosslinking of wild-type DT40 cells. Thus, expression of BCR at the cell surface is likely to be important for the signal cascade initiated by MHC-I crosslinking. Our data suggest that signal transduction initiated through ligation of the MHC-I molecule plays a role in the regulation of B cell homeostasis.

AB - Crosslinking of major histocompatibility complex class I (MHC-I) molecules on the surface of human B lymphoma cells was shown to induce protein tyrosine phosphorylation and mobilization of intracellular free calcium. Immunoprecipitations indicated that the protein tyrosine kinases p53/56lyn and p72syk are among the tyrosine-phosphorylated proteins. The kinetics of phosphorylation of these kinases after MHC-I crosslinking differ from the kinetics observed after crosslinking of the B cell antigen receptor (BCR). Additional experiments were performed with chicken lyn- and syk-negative DT40 B cells and the results indicate that these two kinases have different substrate specificity and regulate intracellular free calcium differently in response to MHC-I crosslinking. In addition MHC-I crosslinking of a sIgM-negative DT40 chicken B cell variant results in less activity of tyrosine kinases and less mobilization of intracellular free calcium compared with MHC-I crosslinking of wild-type DT40 cells. Thus, expression of BCR at the cell surface is likely to be important for the signal cascade initiated by MHC-I crosslinking. Our data suggest that signal transduction initiated through ligation of the MHC-I molecule plays a role in the regulation of B cell homeostasis.

U2 - 10.1006/excr.1998.4014

DO - 10.1006/excr.1998.4014

M3 - Journal article

C2 - 9570929

SN - 0014-4827

VL - 240

SP - 144

EP - 150

JO - Experimental Cell Research

JF - Experimental Cell Research

IS - 1

ER -