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PMID:11672542

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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

Significance

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


See also

References

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