Protein tyrosine kinases p53/56lyn and p72syk in MHC class I-mediated signal transduction in B lymphoma cells.
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.
Pedersen
A E
AE
Department of Medical Anatomy, Panum Institute, University of Copenhagen, Denmark.
Bregenholt
S
S
Skov
S
S
Vrang
M L
ML
Claesson
M H
MH
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002645:Chickens; D003432:Cross-Linking Reagents / Q000378:metabolism; D004792:Enzyme Precursors / Q000378:metabolism*; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D016393:Lymphoma, B-Cell / Q000201:enzymology*; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D015398:Signal Transduction / Q000276:immunology*; D000072377:Syk Kinase; D014407:Tumor Cells, Cultured / Q000201:enzymology / Q000276:immunology; D019061:src-Family Kinases / Q000378:metabolism*
D003432:Cross-Linking Reagents; D004792:Enzyme Precursors; D015395:Histocompatibility Antigens Class I; D047908:Intracellular Signaling Peptides and Proteins; D011505:Protein-Tyrosine Kinases; C000606896:SYK protein, human; D000072377:Syk Kinase; C060902:lyn protein-tyrosine kinase; D019061:src-Family Kinases; D002118:Calcium