![]() Lyn’s SH3 domain can bind an intramolecular proline-motif situated between the SH2 and kinase domains (hinge region), helping generate a stabilized inactive kinase confirmation. In its inactive state Lyn is phosphorylated at its carboxyl terminus by C-terminal Src kinase (Csk) creating a binding site for its own SH2 domain. As with other Src family kinases Lyn is regulated by protein interactions through its SH2/SH3 domains as well as via phosphorylation status (Figure 1A). The reversible N-terminal lipid modification (palmitoylation) and isoform specific pY32 motif potentially complicate understanding Lyn’s function through their latent ability to regulate activity, interactions, and subcellular localization. Lyn has two splice variants (via exon 2) that result in the generation of p53 and p56 kDa protein isoforms, designated as LynA (p56) and LynB (p53), which differ by a 20 amino acid region in the SH4 domain that encompasses a pY motif (pY32). Fyn) palmitoylation sites, followed by homologous domains for protein interaction (SH3 and SH2), as well as a kinase (SH1) domain (Figure 1). Each member has a unique N-terminal region (SH4) encoding a myristoylation site, and may contain one (e.g. Lyn is a member of the Src family of intracellular membrane-associated tyrosine kinases (SFK). Members of the Src family of tyrosine kinases are signaling intermediates that can control aspects of these and other biological processes. Consequently, targeting this protein in these cancers could also prove to be beneficial.īoth receptor and non-receptor protein tyrosine kinases are essential enzymes in many cellular signaling processes regulating cell growth, differentiation, apoptosis, migration, immune responses, adhesion and metabolism. ![]() prostate, brain and breast cancer can also have abnormal regulation of Lyn. Furthermore, some specific types, and even specific subtypes, of solid cancers, e.g. Certain types of leukaemia and lymphoma appear to have too much Lyn activity that in part causes the characteristics of these diseases, suggesting it may be a good target to develop new anti-leukaemia drugs. Lyn has important functions for cells involved in blood development, including different while blood cells as well as red blood cells, and in particular for the immune cells that produce antibodies (B-cells), as exemplified by the major B-cell abnormalities that mice with mutations in the Lyn gene display. This ability of Lyn to be able to both turn on and turn off the relay of information inside cells makes it difficult to fully understand its precise function in each specific circumstance. Depending on which type of cell and the source of the information input, Lyn can positively or negatively regulate the information output. A protein called Lyn is one of these enzymes that regulate information transfer within cells to modulate cell growth, survival and movement. To relay information, a cell uses enzymes that put molecular markers on specific proteins so they interact with other proteins or move to specific parts of the cell to have particular functions. Lyn is also expressed in some solid tumors and here too it is establishing itself as a potential therapeutic target for prostate, glioblastoma, colon and more aggressive subtypes of breast cancer. Lyn has also been found to be important for maintaining the leukemic phenotype of many different liquid cancers including acute myeloid leukaemia (AML), chronic myeloid leukaemia (CML) and B-cell lymphocytic leukaemia (BCLL). Lyn is an important regulator of autoimmune diseases such as asthma and psoriasis, due to its profound ability to influence immune cell signaling. Consequently, there is an important role for this kinase in regulating hematopoietic abnormalities. erythrocytes, platelets, mast cells and macrophages. progenitors via influencing c-kit signaling, through to mature cell receptor/integrin signaling, e.g. Lyn has well-established functions in most haematopoietic cells, viz. ![]() This duality is exemplified by the B-cell defect in Lyn −/− mice in which Lyn is essential for negative regulation of the B-cell receptor conversely, B-cells expressing a dominant active mutant of Lyn ( Lyn up/up) have elevated activities of positive regulators of the B-cell receptor due to this hyperactive kinase. Intriguingly, Lyn can mediate both positive and negative signaling processes within the same or different cellular contexts. Src family kinases such as Lyn are important signaling intermediaries, relaying and modulating different inputs to regulate various outputs, such as proliferation, differentiation, apoptosis, migration and metabolism.
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