PMID:11672542

Citation	Harder, KW, Parsons, LM, Armes, J, Evans, N, Kountouri, N, Clark, R, Quilici, C, Grail, D, Hodgson, GS, Dunn, AR and Hibbs, ML (2001) Gain- and loss-of-function Lyn mutant mice define a critical inhibitory role for Lyn in the myeloid lineage. Immunity 15:603-15
Abstract	To investigate the role of the Lyn kinase in establishing signaling thresholds in hematopoietic cells, a gain-of-function mutation analogous to the Src Y527F-activating mutation was introduced into the Lyn gene. Intriguingly, although Lyn is widely expressed within the hematopoietic system, these mice displayed no propensity toward hematological malignancy. By contrast, analysis of aging cohorts of both loss- and gain-of-function Lyn mutant mice revealed that Lyn(-/-) mice develop splenomegaly, increased numbers of myeloid progenitors, and monocyte/macrophage (M phi) tumors. Biochemical analysis of cells from these mutants revealed that Lyn is essential in establishing ITIM-dependent inhibitory signaling and for activation of specific protein tyrosine phosphatases within myeloid cells. Loss of such inhibitory signaling may predispose mice lacking this putative protooncogene to tumorigenesis.
Links	PubMed
Keywords	Aging; Animals; Bone Marrow Cells/physiology; Cell Lineage; Cells, Cultured; Colony-Stimulating Factors/pharmacology; Hematologic Neoplasms/etiology; Hematologic Neoplasms/pathology; Macrophages/physiology; Mice; Mice, Knockout; Mice, SCID; Models, Biological; Mutation; Myeloid Cells/physiology; Myeloid Progenitor Cells/physiology; Protein Tyrosine Phosphatases/metabolism; Spleen/pathology; Splenomegaly/etiology; Splenomegaly/pathology; src-Family Kinases/genetics; src-Family Kinases/physiology
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
MOUSE:LYN	involved_in	GO:0030097: hemopoiesis	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
MOUSE:LYN	involved_in	GO:0002762: negative regulation of myeloid leukocyte differentiation	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
MOUSE:LYN	enables	GO:0004713: protein tyrosine kinase activity	ECO:0000314: direct assay evidence used in manual assertion		F		Seeded From UniProt	complete
MOUSE:LYN	involved_in	GO:0018108: peptidyl-tyrosine phosphorylation	ECO:0000314: direct assay evidence used in manual assertion		P		Seeded From UniProt	complete
MOUSE:LYN	involved_in	GO:0046777: protein autophosphorylation	ECO:0000314: direct assay evidence used in manual assertion		P		Seeded From UniProt	complete
MOUSE:LYN	involved_in	GO:0050855: regulation of B cell receptor signaling pathway	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete

References

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