Recombinant Human Tyrosine-protein kinase Lyn (LYN)

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. Involved in the regulation of endothelial activation, neutrophil adhesion and transendothelial migration (PubMed:36932076). 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). Phosphorylates BCAR1/CAS and NEDD9/HEF1 (PubMed:9020138)

Subcellular Location

Cell membrane; Nucleus; Cytoplasm; Cytoplasm, perinuclear region; Golgi apparatus; Membrane (Lipid-anchor)

Disease Association

Autoinflammatory disease, systemic, with vasculitis (SAIDV) : An autosomal dominant disorder characterized by systemic autoinflammation manifesting in the first hours of life with diffuse purpuric skin lesions, fever, hepatosplenomegaly, and increased C-reactive protein. Additional clinical features include periorbital edema, conjunctivitis, urticaria, atopic dermatitis, abdominal pain, and arthralgia. Laboratory studies may show leukocytosis, thrombocytopenia, and autoantibodies. [The disease is caused by variants affecting the gene represented in this entry] | [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]

Tissue Specificity

Detected in monocytes (at protein level). Detected in placenta, and in fetal brain, lung, liver and kidney. Widely expressed in a variety of organs, tissues, and cell types such as epidermoid, hematopoietic, and neuronal cells. Expressed in primary neuroblastoma tumors

Subunit

(Microbial infection) Interacts with Herpes virus saimiri tyrosine kinase interacting protein (Tip)

• Yamanashi Y. et al. The yes-related cellular gene lyn encodes a possible tyrosine kinase similar to p56lck. — Mol. Cell. Biol. (1987)
• Rider L.G. et al. The cDNAs encoding two forms of the LYN protein tyrosine kinase are expressed in rat mast cells and human myeloid cells. — Gene (1994)
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). — Genome Res. (2004)
• Partanen J. et al. Putative tyrosine kinases expressed in K-562 human leukemia cells. — Proc. Natl. Acad. Sci. U.S.A. (1990)
• Bielke W. et al. Expression of the B cell-associated tyrosine kinase gene Lyn in primary neuroblastoma tumours and its modulation during the differentiation of neuroblastoma cell lines. — Biochem. Biophys. Res. Commun. (1992)
• Roifman C.M. et al. CD19 is a substrate of the antigen receptor-associated protein tyrosine kinase in human B cells. — Biochem. Biophys. Res. Commun. (1993)
• Yamanashi Y. et al. Identification of HS1 protein as a major substrate of protein-tyrosine kinase(s) upon B-cell antigen receptor-mediated signaling. — Proc. Natl. Acad. Sci. U.S.A. (1993)
• Wang A.V. et al. Physical and functional association of the high affinity immunoglobulin G receptor (Fc gamma RI) with the kinases Hck and Lyn. — J. Exp. Med. (1994)