Lyn tyrosine kinase: accentuating the positive and the negative.
Lyn, one of several Src-family tyrosine kinases in immune cells, is noted for its ability to negatively regulate signaling pathways through phosphorylation of inhibitory receptors, enzymes, and adaptors. Somewhat paradoxically, it is also a key mediator in several pathways of B cell activation, such as CD19 and CD180. Whether Lyn functions to promote or inhibit immune cell activation depends on the stimulus and the developmental state, meaning that the consequences of Lyn activity are context dependent. The importance of regulating Lyn activity is exemplified by the pathological conditions that develop in both lyn-/- and lyn gain-of-function mice (lynup/up), including lethal antibody-mediated autoimmune diseases and myeloid neoplasia. Here, we review the outcomes of altered Lyn activity within the framework of B cell development and differentiation and the circumstances that appear to dictate the outcome.
Xu
Yuekang
Y
The Walter and Eliza Hall Institute of Medical Research, Melbourne 3050, Australia.
Harder
Kenneth W
KW
Huntington
Nicholas D
ND
Hibbs
Margaret L
ML
Tarlinton
David M
DM
D000818:Animals; D001327:Autoimmune Diseases / Q000201:enzymology / Q000378:metabolism; D001402:B-Lymphocytes / Q000166:cytology / Q000201:enzymology* / Q000378:metabolism; D002454:Cell Differentiation; D004792:Enzyme Precursors / Q000378:metabolism; D005816:Genetic Complementation Test; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D008822:Mice, Transgenic; D008954:Models, Biological; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051562:Proto-Oncogene Proteins c-bcr; D015398:Signal Transduction; D000072377:Syk Kinase; D019061:src-Family Kinases / Q000378:metabolism*
D004792:Enzyme Precursors; D047908:Intracellular Signaling Peptides and Proteins; D011518:Proto-Oncogene Proteins; D011505:Protein-Tyrosine Kinases; D000072377:Syk Kinase; C000606897:Syk protein, mouse; C060902:lyn protein-tyrosine kinase; D019061:src-Family Kinases; C496614:Bcr protein, mouse; D051562:Proto-Oncogene Proteins c-bcr