LYN

LYN is a tyrosine protein kinase, which maybe involved in the regulation of mast cell degranulation, and erythroid differentiation.

LYN

Non-receptor tyrosine-protein kinase that transmits signals from cell surface receptors and plays an important role in the regulation of innate and adaptive immune responses, hematopoiesis, responses to growth factors and cytokines, integrin signaling, but also responses to DNA damage and genotoxic agents. Functions primarily as negative regulator, but can also function as activator, depending on the context. Required for the initiation of the B-cell response, but also for its down-regulation and termination. Plays an important role in the regulation of B-cell differentiation, proliferation, survival and apoptosis, and is important for immune self-tolerance. Acts downstream of several immune receptors, including the B-cell receptor, CD79A, CD79B, CD5, CD19, CD22, FCER1, FCGR2, FCGR1A, TLR2 and TLR4. Plays a role in the inflammatory response to bacterial lipopolysaccharide. Mediates the responses to cytokines and growth factors in hematopoietic progenitors, platelets, erythrocytes, and in mature myeloid cells, such as dendritic cells, neutrophils and eosinophils. Acts downstream of EPOR, KIT, MPL, the chemokine receptor CXCR4, as well as the receptors for IL3, IL5 and CSF2. Plays an important role in integrin signaling. Regulates cell proliferation, survival, differentiation, migration, adhesion, degranulation, and cytokine release. Down-regulates signaling pathways by phosphorylation of immunoreceptor tyrosine-based inhibitory motifs (ITIM), that then serve as binding sites for phosphatases, such as PTPN6/SHP-1, PTPN11/SHP-2 and INPP5D/SHIP-1, that modulate signaling by dephosphorylation of kinases and their substrates. Phosphorylates LIME1 in response to CD22 activation. Phosphorylates BTK, CBL, CD5, CD19, CD72, CD79A, CD79B, CSF2RB, DOK1, HCLS1, LILRB3/PIR-B, MS4A2/FCER1B, SYK and TEC. Promotes phosphorylation of SIRPA, PTPN6/SHP-1, PTPN11/SHP-2 and INPP5D/SHIP-1. Mediates phosphorylation of the BCR-ABL fusion protein. Required for rapid phosphorylation of FER in response to FCER1 activation. Mediates KIT phosphorylation. Acts as an effector of EPOR (erythropoietin receptor) in controlling KIT expression and may play a role in erythroid differentiation during the switch between proliferation and maturation. Depending on the context, activates or inhibits several signaling cascades. Regulates phosphatidylinositol 3-kinase activity and AKT1 activation. Regulates activation of the MAP kinase signaling cascade, including activation of MAP2K1/MEK1, MAPK1/ERK2, MAPK3/ERK1, MAPK8/JNK1 and MAPK9/JNK2. Mediates activation of STAT5A and/or STAT5B. Phosphorylates LPXN on 'Tyr-72'. Kinase activity facilitates TLR4-TLR6 heterodimerization and signal initiation. Phosphorylates SCIMP on 'Tyr-107'; this enhances binding of SCIMP to TLR4, promoting the phosphorylation of TLR4, and a selective cytokine response to lipopolysaccharide in macrophages (By similarity).
Phosphorylates CLNK (By similarity).

Adaptive immune responseIEA:UniProtKB-KW
B cell homeostasisISS:UniProtKB
B cell receptor signaling pathwayIEA:Ensembl
Cell differentiationManual Assertion Based On ExperimentIBA:GO_Central
Cellular response to DNA damage stimulusManual Assertion Based On ExperimentIDA:UniProtKB
Cellular response to extracellular stimulusIEA:Ensembl
Cellular response to heatIEA:Ensembl
Cellular response to retinoic acidManual Assertion Based On ExperimentIMP:BHF-UCL
Dendritic cell differentiationISS:UniProtKB
Ephrin receptor signaling pathwayTAS:Reactome
Erythrocyte differentiationISS:UniProtKB
Fc receptor mediated inhibitory signaling pathwayISS:UniProtKB
Fc receptor mediated stimulatory signaling pathwayISS:UniProtKB
Fc-epsilon receptor signaling pathwayTAS:Reactome
Fc-gamma receptor signaling pathway involved in phagocytosisTAS:Reactome
Growth hormone receptor signaling pathway via JAK-STATTAS:Reactome
Histamine secretion by mast cellIEA:Ensembl
Immune response-regulating cell surface receptor signaling pathwayISS:UniProtKB
Innate immune responseManual Assertion Based On ExperimentIBA:GO_Central
Intracellular signal transductionIEA:Ensembl
Leukocyte migrationTAS:Reactome
Lipopolysaccharide-mediated signaling pathwayISS:UniProtKB
Negative regulation of B cell proliferationManual Assertion Based On ExperimentIBA:GO_Central
Negative regulation of cell population proliferationManual Assertion Based On ExperimentIMP:UniProtKB
Negative regulation of ERK1 and ERK2 cascadeISS:UniProtKB
Negative regulation of immune responseManual Assertion Based On ExperimentTAS:UniProtKB
Negative regulation of inflammatory response to antigenic stimulusTAS:Reactome
Negative regulation of intracellular signal transductionISS:UniProtKB
Negative regulation of MAP kinase activityISS:UniProtKB
Negative regulation of mast cell proliferationISS:UniProtKB
Negative regulation of myeloid leukocyte differentiationIEA:Ensembl
Negative regulation of protein phosphorylationISS:UniProtKB
Negative regulation of toll-like receptor 2 signaling pathwayISS:UniProtKB
Negative regulation of toll-like receptor 4 signaling pathwayISS:UniProtKB
Neuron projection developmentManual Assertion Based On ExperimentIBA:GO_Central
Oligodendrocyte developmentIEA:Ensembl
Peptidyl-tyrosine phosphorylationManual Assertion Based On ExperimentIDA:UniProtKB
Platelet degranulationISS:UniProtKB
Positive regulation of aspartic-type endopeptidase activity involved in amyloid precursor protein catabolic processManual Assertion Based On ExperimentIMP:ARUK-UCL
Positive regulation of cell migrationIEA:Ensembl
Positive regulation of cell population proliferationISS:UniProtKB
Positive regulation of cellular component movementManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of dendritic cell apoptotic processISS:UniProtKB
Positive regulation of Fc receptor mediated stimulatory signaling pathwayIEA:Ensembl
Positive regulation of glial cell proliferationIEA:Ensembl
Positive regulation of mast cell proliferationManual Assertion Based On ExperimentIMP:UniProtKB
Positive regulation of neuron projection developmentManual Assertion Based On ExperimentIMP:BHF-UCL
Positive regulation of oligodendrocyte progenitor proliferationIEA:Ensembl
Positive regulation of phosphatidylinositol 3-kinase activityIEA:Ensembl
Positive regulation of protein phosphorylationManual Assertion Based On ExperimentIGI:ARUK-UCL
Positive regulation of stress-activated protein kinase signaling cascadeManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of tyrosine phosphorylation of STAT proteinISS:UniProtKB
Protein autophosphorylationManual Assertion Based On ExperimentIDA:UniProtKB
Protein phosphorylationManual Assertion Based On ExperimentIDA:UniProtKB
Regulation of B cell apoptotic processManual Assertion Based On ExperimentIBA:GO_Central
Regulation of B cell receptor signaling pathwayISS:UniProtKB
Regulation of cell adhesion mediated by integrinManual Assertion Based On ExperimentIMP:UniProtKB
Regulation of cytokine productionISS:UniProtKB
Regulation of ERK1 and ERK2 cascadeISS:UniProtKB
Regulation of erythrocyte differentiationISS:UniProtKB
Regulation of mast cell activationISS:UniProtKB
Regulation of mast cell degranulationISS:UniProtKB
Regulation of monocyte chemotaxisManual Assertion Based On ExperimentIMP:UniProtKB
Regulation of platelet aggregationISS:UniProtKB
Regulation of protein phosphorylationManual Assertion Based On ExperimentTAS:UniProtKB
Regulation of release of sequestered calcium ion into cytosolIEA:Ensembl
Response to amino acidIEA:Ensembl
Response to axon injuryIEA:Ensembl
Response to carbohydrateIEA:Ensembl
Response to hormoneISS:UniProtKB
Response to insulinIEA:Ensembl
Response to organic cyclic compoundIEA:Ensembl
Response to sterol depletionIEA:Ensembl
Response to toxic substanceIEA:Ensembl
Response to xenobiotic stimulusIEA:Ensembl
Signal transductionManual Assertion Based On ExperimentTAS:ProtInc
Stimulatory C-type lectin receptor signaling pathwayTAS:Reactome
T cell costimulationTAS:Reactome
Tolerance induction to self antigenISS:UniProtKB
Toll-like receptor 4 signaling pathwayIEA:Ensembl
Transmembrane receptor protein tyrosine kinase signaling pathwayManual Assertion Based On ExperimentIMP:UniProtKB

Cell membrane
Nucleus
Cytoplasm
Cytoplasm, perinuclear region
Golgi apparatus
Membrane
Accumulates in the nucleus by inhibition of CRM1-mediated nuclear export. Nuclear accumulation is increased by inhibition of its kinase activity. The trafficking from the Golgi apparatus to the plasma membrane occurs in a kinase domain-dependent but kinase activity independent manner and is mediated by exocytic vesicular transport. Detected on plasma membrane lipid rafts.

Constitutively phosphorylated and activated in cells from a number of chronic myelogenous leukemia (CML) and acute myeloid leukemia (AML) patients. Mediates phosphorylation of the BCR-ABL fusion protein. Abnormally elevated expression levels or activation of LYN signaling may play a role in survival and proliferation of some types of cancer cells.

Ubiquitinated by CBL, leading to its degradation. Ubiquitination is SH3-dependent.
Autophosphorylated. Phosphorylated on tyrosine residues in response to KIT signaling. Phosphorylation at Tyr-397 is required for optimal activity. Phosphorylation at Tyr-508 inhibits kinase activity. Phosphorylated at Tyr-508 by CSK. Dephosphorylated by PTPRC/CD45. Becomes rapidly phosphorylated upon activation of the B-cell receptor and the immunoglobulin receptor FCGR1A.