LYN
Description
The LYN (LYN proto-oncogene, Src family tyrosine kinase) is a protein-coding gene located on chromosome 8.
Tyrosine-protein kinase Lyn is a protein that in humans is encoded by the LYN gene. Lyn is a member of the Src family of protein tyrosine kinases, which is mainly expressed in hematopoietic cells, in neural tissues liver, and adipose tissue. In various hematopoietic cells, Lyn has emerged as a key enzyme involved in the regulation of cell activation. In these cells, a small amount of LYN is associated with cell surface receptor proteins, including the B cell antigen receptor (BCR), CD40, or CD19. The abbreviation Lyn is derived from Lck/Yes novel tyrosine kinase, Lck and Yes also being members of the Src kinase family.
== Function == Lyn has been described to have an inhibitory role in myeloid lineage proliferation. Following engagement of the B cell receptors, Lyn undergoes rapid phosphorylation and activation. LYN activation triggers a cascade of signaling events mediated by Lyn phosphorylation of tyrosine residues within the immunoreceptor tyrosine-based activation motifs (ITAM) of the receptor proteins, and subsequent recruitment and activation of other kinases including Syk, phosholipase Cγ2 (PLCγ2) and phosphatidyl inositol-3 kinase. These kinases provide activation signals, which play critical roles in proliferation, Ca2+ mobilization and cell differentiation. Lyn plays an essential role in the transmission of inhibitory signals through phosphorylation of tyrosine residues within the immunoreceptor tyrosine-based inhibitory motifs (ITIM) in regulatory proteins such as CD22, PIR-B and FCγRIIb1.
LYN, also known as Lck/Yes-related novel protein tyrosine kinase, V-yes-1 Yamaguchi sarcoma viral related oncogene homolog, p53Lyn, p56Lyn, is a non-receptor tyrosine-protein kinase that transmits signals from cell surface receptors. It plays a crucial role in regulating innate and adaptive immune responses, hematopoiesis, responses to growth factors and cytokines, integrin signaling, and responses to DNA damage and genotoxic agents. LYN primarily acts as a negative regulator, but can also function as an activator depending on the context. It is essential for the initiation of the B-cell response, but also for its down-regulation and termination. LYN plays a significant role in regulating B-cell differentiation, proliferation, survival, and apoptosis, and is crucial for immune self-tolerance. It acts downstream of various immune receptors, including the B-cell receptor, CD79A, CD79B, CD5, CD19, CD22, FCER1, FCGR2, FCGR1A, TLR2, and TLR4. LYN participates in the inflammatory response to bacterial lipopolysaccharide. It mediates responses to cytokines and growth factors in hematopoietic progenitors, platelets, erythrocytes, and mature myeloid cells like dendritic cells, neutrophils, and eosinophils. LYN acts downstream of EPOR, KIT, MPL, the chemokine receptor CXCR4, as well as the receptors for IL3, IL5, and CSF2. It plays a significant role in integrin signaling, regulating cell proliferation, survival, differentiation, migration, adhesion, degranulation, and cytokine release. LYN is involved in the regulation of endothelial activation, neutrophil adhesion, and transendothelial migration. It downregulates signaling pathways by phosphorylating immunoreceptor tyrosine-based inhibitory motifs (ITIM), which then serve as binding sites for phosphatases like PTPN6/SHP-1, PTPN11/SHP-2, and INPP5D/SHIP-1, modulating signaling by dephosphorylating kinases and their substrates. LYN phosphorylates LIME1 in response to CD22 activation. It also phosphorylates BTK, CBL, CD5, CD19, CD72, CD79A, CD79B, CSF2RB, DOK1, HCLS1, LILRB3/PIR-B, MS4A2/FCER1B, SYK, and TEC. LYN promotes the phosphorylation of SIRPA, PTPN6/SHP-1, PTPN11/SHP-2, and INPP5D/SHIP-1. It mediates phosphorylation of the BCR-ABL fusion protein and is required for rapid phosphorylation of FER in response to FCER1 activation. LYN mediates KIT phosphorylation and acts as an effector of EPOR (erythropoietin receptor) in controlling KIT expression, potentially playing a role in erythroid differentiation during the switch between proliferation and maturation. Depending on the context, LYN activates or inhibits various signaling cascades. It regulates phosphatidylinositol 3-kinase activity and AKT1 activation. It regulates activation of the MAP kinase signaling cascade, including activation of MAP2K1/MEK1, MAPK1/ERK2, MAPK3/ERK1, MAPK8/JNK1, and MAPK9/JNK2. LYN mediates activation of STAT5A and/or STAT5B. It phosphorylates LPXN on ‘Tyr-72‘. Its kinase activity facilitates TLR4-TLR6 heterodimerization and signal initiation. LYN phosphorylates SCIMP on ‘Tyr-107‘, enhancing the binding of SCIMP to TLR4, promoting the phosphorylation of TLR4, and a selective cytokine response to lipopolysaccharide in macrophages. LYN phosphorylates CLNK, BCAR1/CAS, and NEDD9/HEF1. LYN interacts with TEC, FLT3 (tyrosine phosphorylated via SH2 domain), LIME1, CD79A upon activation of the B-cell antigen receptor, the B-cell receptor complex, phosphorylated THEMIS2, EPOR, MS4A2/FCER1B, MUC1 (via the SH2 and SH3 domains, stimulated by IL7, the subsequent phosphorylation increases the binding between MUC1 and CTNNB1/beta-catenin), ADAM15, NDFIP2, NDFIP1, FASLG, KIT, HCLS1, FCGR2B, FCGR1A (the interaction may be indirect), CD19, CD22, CD79A, CD79B, CBLC (via SH3 domain), PPP1R15A (via SH3 domain), PDE4A (via SH3 domain), TGFB1I1, PIK3R1 (the regulatory subunit of phosphatidylinositol 3-kinase via SH3 domain, this interaction enhances phosphatidylinositol 3-kinase activity), CSF2RB (the common subunit of the IL3, IL5, and CSF2 receptors), PAG1 (identified in a complex with PAG1 and STAT3), ABL1, PTPN6/SHP-1, SCIMP (via SH3 domain, via proline-rich region, this interaction facilitates the phosphorylation of SCIMP on ‘Tyr-107‘, which enhances binding of SCIMP to TLR4, and consequently the phosphorylation of TLR4 in response to stimulation by lipopolysaccharide in macrophages), LPXN (via LD motif 3, the interaction is induced upon B-cell antigen receptor (BCR) activation), ANKRD54 (via SH3-domain, via ankyrin repeat region, in an activation-independent status of LYN, forming a multiprotein complex with ANKRD54 and HCLS1), UNC119 (via SH2 and SH3 domains, leading to LYN activation), CD36, LYN (By similarity), SKAP1, FYB1 (this interaction promotes the phosphorylation of CLNK), BCAR1/CAS, NEDD9/HEF1. LYN interacts with Epstein-Barr virus LMP2A, Herpes virus saimiri tyrosine kinase interacting protein (Tip).
LYN is also known as JTK8, SAIDV, p53Lyn, p56Lyn.
