LYN / TRP channels
Name: Tyrosine-protein kinase Lyn
(LYN)
Official Symbol: LYN
provided by HGNC
Function:
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, PTK2B/PYK2, 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'.
Source: Reorganizing the protein space at the Universal Protein Resource (UniProt)
Nucleic Acids Res. 40: D71-D75 (2012).
Species | External DB | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Entrez Gene | UniprotKB | DIP | IntAct | MINT | BioGRID | STRING | IUPHAR-DB | KEGG | OMIM | |
Human
|
4067 | P07948 | DIP-1056N | P07948 | MINT-200655 | 110245 | P07948 | hsa:4067 | 165120 | |
Mouse
|
17096 | P25911 | DIP-37806N | P25911 | MINT-100482 | 201256 | P25911 | mmu:17096 | ||
Rat
|
81515 | Q07014 | MINT-4564766 | 249512 | Q07014 | rno:81515 |
Biological Process:
- GO:0001782 : B cell homeostasis
- GO:0050853 : B cell receptor signaling pathway
- GO:0031668 : cellular response to extracellular stimulus
- GO:0034605 : cellular response to heat
- GO:0071300 : cellular response to retinoic acid
- GO:0050663 : cytokine secretion
- GO:0097028 : dendritic cell differentiation
- GO:0030218 : erythrocyte differentiation
- GO:0002774 : Fc receptor mediated inhibitory signaling pathway
- GO:0002431 : Fc receptor mediated stimulatory signaling pathway
- GO:0002553 : histamine secretion by mast cell
- GO:0045087 : innate immune response
- GO:0060397 : JAK-STAT cascade involved in growth hormone signaling pathway
- GO:0050900 : leukocyte migration
- GO:0031663 : lipopolysaccharide-mediated signaling pathway
- GO:0030889 : negative regulation of B cell proliferation
- GO:0070373 : negative regulation of ERK1 and ERK2 cascade
- GO:0050777 : negative regulation of immune response
- GO:0043407 : negative regulation of MAP kinase activity
- GO:0070667 : negative regulation of mast cell proliferation
- GO:0002762 : negative regulation of myeloid leukocyte differentiation
- GO:0034136 : negative regulation of toll-like receptor 2 signaling pathway
- GO:0034144 : negative regulation of toll-like receptor 4 signaling pathway
- GO:0031175 : neuron projection development
- GO:0014003 : oligodendrocyte development
- GO:0018108 : peptidyl-tyrosine phosphorylation
- GO:0030168 : platelet activation
- GO:0002576 : platelet degranulation
- GO:0030335 : positive regulation of cell migration
- GO:0051272 : positive regulation of cellular component movement
- GO:2000670 : positive regulation of dendritic cell apoptotic process
- GO:0060369 : positive regulation of Fc receptor mediated stimulatory signaling pathway
- GO:0060252 : positive regulation of glial cell proliferation
- GO:0070668 : positive regulation of mast cell proliferation
- GO:0010976 : positive regulation of neuron projection development
- GO:0070447 : positive regulation of oligodendrocyte progenitor proliferation
- GO:0043552 : positive regulation of phosphatidylinositol 3-kinase activity
- GO:0070304 : positive regulation of stress-activated protein kinase signaling cascade
- GO:0042531 : positive regulation of tyrosine phosphorylation of STAT protein
- GO:0046777 : protein autophosphorylation
- GO:0002902 : regulation of B cell apoptotic process
- GO:0050855 : regulation of B cell receptor signaling pathway
- GO:0033628 : regulation of cell adhesion mediated by integrin
- GO:0001817 : regulation of cytokine production
- GO:0050707 : regulation of cytokine secretion
- GO:0045646 : regulation of erythrocyte differentiation
- GO:0050727 : regulation of inflammatory response
- GO:0043304 : regulation of mast cell degranulation
- GO:0090025 : regulation of monocyte chemotaxis
- GO:0090330 : regulation of platelet aggregation
- GO:0051279 : regulation of release of sequestered calcium ion into cytosol
- GO:0043200 : response to amino acid stimulus
- GO:0048678 : response to axon injury
- GO:0009743 : response to carbohydrate stimulus
- GO:0006974 : response to DNA damage stimulus
- GO:0032868 : response to insulin stimulus
- GO:0014070 : response to organic cyclic compound
- GO:0006991 : response to sterol depletion
- GO:0009636 : response to toxin
- GO:0031295 : T cell costimulation
- GO:0002513 : tolerance induction to self antigen
- GO:0019048 : virus-host interaction
Source: The Gene Ontology Consortium. Gene ontology: tool for the unification of biology. Nat. Genet.. May 2000;25(1):25-9.
World Wide Web URL: http://www.geneontology.org/
World Wide Web URL: http://www.geneontology.org/
Disease:
No information in OMIM
Source: Online Mendelian Inheritance in Man, OMIM®. McKusick-Nathans Institute of Genetic Medicine,
Johns Hopkins University (Baltimore, MD), May, 2012.
World Wide Web URL: http://omim.org/
World Wide Web URL: http://omim.org/
Screening Validation: In vitro validation Validation: In vivo validation Characterization Functional consequence | top |
Screening | ||||||||||
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Experimental screening | Non-experimental screening | Reference | ||||||||
TRP channel construct | Interactor source | |||||||||
TRP channel | Interactor | Method | Species | Region | Species | Organ/tissue | Sample type | |||
TRPC4 | LYN | Inference | Prediction | 16144838 | ||||||
TRPV4 | LYN | Inference | Prediction | 12538589 |
(:
click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)
Screening Validation: In vitro validation Validation: In vivo validation Characterization Functional consequence | top |
Validation: In vivo validation | ||||||||||
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Assay with endogenous proteins | Assay with overexpressed proteins | Reference | ||||||||
Cell or tissue | Cell or tissue | TRP channel construct | Interactor construct | |||||||
TRP channel | Interactor | Method | Species | Region | Species | Region | ||||
TRPC4 | LYN | Co-immunoprecipitation | COS-7 | 16144838 | ||||||
TRPC4 | LYN | Co-immunoprecipitation | COS-7 | Human | Full-length | Not specifed | Full-length | 16144838 | ||
TRPV4 | LYN | Co-immunofluorescence staining | HEK293 | Mouse | Full-length | Not used | 12538589 | |||
TRPV4 | LYN | Co-immunoprecipitation | Rat dorsal root ganglion neuron | 18234883 | ||||||
TRPV4 | LYN | Co-immunoprecipitation | HEK293 | Mouse | Full-length | Mouse | Full-length | 12538589 |
(:
click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)
Screening Validation: In vitro validation Validation: In vivo validation Characterization Functional consequence | top |
Functional consequence | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
TRP channel | Interactor | Method | Post-translational modification | Subcellular trafficking | Activity | Reference | ||||||
TRPV4 | LYN | Calcium measurement | Activation | 12538589 | ||||||||
TRPV4 | LYN | In vitro PTM assay | Phosphorylation (Tyr-273) | 12538589 |
(:
click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)