Target Information
Target General Infomation | |||||
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Target ID |
T68163
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Former ID |
TTDI02273
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Target Name |
Lyn tyrosine kinase
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Gene Name |
LYN
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Synonyms |
Lck/Yes-related novel protein tyrosine kinase; Tyrosine-protein kinase Lyn; V-yes-1 Yamaguchi sarcoma viral related oncogene homolog; p53Lyn; p56Lyn; LYN
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Target Type |
Clinical Trial
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Disease | Bone disease; Chronic lymphocytic leukaemia; Metastatic hormone refractory prostate cancer [ICD9:185; ICD10: M00-M99, C91, C61] | ||||
Cancer [ICD9: 140-229; ICD10: C00-C96] | |||||
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'. Kinase activity facilitates TLR4-TLR6 heterodimerization and signal initiation.
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BioChemical Class |
Kinase
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UniProt ID | |||||
EC Number |
EC 2.7.10.2
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Sequence |
MGCIKSKGKDSLSDDGVDLKTQPVRNTERTIYVRDPTSNKQQRPVPESQLLPGQRFQTKD
PEEQGDIVVALYPYDGIHPDDLSFKKGEKMKVLEEHGEWWKAKSLLTKKEGFIPSNYVAK LNTLETEEWFFKDITRKDAERQLLAPGNSAGAFLIRESETLKGSFSLSVRDFDPVHGDVI KHYKIRSLDNGGYYISPRITFPCISDMIKHYQKQADGLCRRLEKACISPKPQKPWDKDAW EIPRESIKLVKRLGAGQFGEVWMGYYNNSTKVAVKTLKPGTMSVQAFLEEANLMKTLQHD KLVRLYAVVTREEPIYIITEYMAKGSLLDFLKSDEGGKVLLPKLIDFSAQIAEGMAYIER KNYIHRDLRAANVLVSESLMCKIADFGLARVIEDNEYTAREGAKFPIKWTAPEAINFGCF TIKSDVWSFGILLYEIVTYGKIPYPGRTNADVMTALSQGYRMPRVENCPDELYDIMKMCW KEKAEERPTFDYLQSVLDDFYTATEGQYQQQP |
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Drugs and Mode of Action | |||||
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM) | |||||
TEP | EXP Info | ||||
Pathways | |||||
KEGG Pathway | Chemokine signaling pathway | ||||
NF-kappa B signaling pathway | |||||
Platelet activation | |||||
B cell receptor signaling pathway | |||||
Fc epsilon RI signaling pathway | |||||
Fc gamma R-mediated phagocytosis | |||||
Long-term depression | |||||
Epithelial cell signaling in Helicobacter pylori infection | |||||
Epstein-Barr virus infection | |||||
Viral carcinogenesis | |||||
NetPath Pathway | IL2 Signaling Pathway | ||||
PANTHER Pathway | B cell activation | ||||
Parkinson disease | |||||
CCKR signaling map ST | |||||
Pathway Interaction Database | Fc-epsilon receptor I signaling in mast cells | ||||
BCR signaling pathway | |||||
LPA receptor mediated events | |||||
GMCSF-mediated signaling events | |||||
Glypican 1 network | |||||
Signaling events mediated by PTP1B | |||||
Regulation of p38-alpha and p38-beta | |||||
Thromboxane A2 receptor signaling | |||||
CXCR4-mediated signaling events | |||||
IL5-mediated signaling events | |||||
Class I PI3K signaling events | |||||
amb2 Integrin signaling | |||||
EPHA forward signaling | |||||
PDGFR-beta signaling pathway | |||||
IL8- and CXCR2-mediated signaling events | |||||
Signaling events mediated by Stem cell factor receptor (c-Kit) | |||||
EPO signaling pathway | |||||
IL8- and CXCR1-mediated signaling events | |||||
Ephrin B reverse signaling | |||||
Alpha-synuclein signaling | |||||
PathWhiz Pathway | Fc Epsilon Receptor I Signaling in Mast Cells | ||||
Reactome | GPVI-mediated activation cascade | ||||
Regulation of KIT signaling | |||||
Cell surface interactions at the vascular wall | |||||
FCGR activation | |||||
PECAM1 interactions | |||||
Fc epsilon receptor (FCERI) signaling | |||||
EPH-Ephrin signaling | |||||
Role of LAT2/NTAL/LAB on calcium mobilization | |||||
FCERI mediated MAPK activation | |||||
FCERI mediated Ca+2 mobilization | |||||
FCERI mediated NF-kB activation | |||||
CD28 co-stimulation | |||||
CTLA4 inhibitory signaling | |||||
EPHB-mediated forward signaling | |||||
EPHA-mediated growth cone collapse | |||||
EPH-ephrin mediated repulsion of cells | |||||
Dectin-2 family | |||||
CD209 (DC-SIGN) signaling | |||||
Platelet Adhesion to exposed collagen | |||||
Regulation of signaling by CBL | |||||
Growth hormone receptor signaling | |||||
Antigen activates B Cell Receptor (BCR) leading to generation of second messengers | |||||
WikiPathways | Kit receptor signaling pathway | ||||
IL-3 Signaling Pathway | |||||
Fc epsilon receptor (FCERI) signaling | |||||
Signaling by the B Cell Receptor (BCR) | |||||
Signaling by SCF-KIT | |||||
Growth hormone receptor signaling | |||||
B Cell Receptor Signaling Pathway | |||||
TSLP Signaling Pathway | |||||
RANKL/RANK Signaling Pathway | |||||
Platelet Adhesion to exposed collagen | |||||
GPVI-mediated activation cascade | |||||
Costimulation by the CD28 family | |||||
Cell surface interactions at the vascular wall | |||||
IL-5 Signaling Pathway | |||||
References | |||||
Ref 522319 | ClinicalTrials.gov (NCT00676299) A Safety and Dose-finding Study of JNJ-26483327, a Drug in Development for Cancer, for Patients With Advanced and/or Refractory Solid Malignancies.. U.S. National Institutes of Health. | ||||
Ref 528928 | Bioorg Med Chem Lett. 2007 Aug 1;17(15):4363-8. Epub 2007 Apr 13.N-4-Pyrimidinyl-1H-indazol-4-amine inhibitors of Lck: indazoles as phenol isosteres with improved pharmacokinetics. |
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