Encyclopedia of Signaling Molecules

2018 Edition
| Editors: Sangdun Choi

Lyn

  • Sai Kundur
  • Hung Nguyen
  • Lloyd McKee
  • Clairissa Cruz
  • Ponniah Selvakumar
  • Ashakumary Lakshmikuttyamma
Reference work entry
DOI: https://doi.org/10.1007/978-3-319-67199-4_101499

Synonyms

Historical Background

Tyrosine kinases play a significant role in different cellular processes such as cell growth, apoptosis, and migration (Ingley 2012; Manning et al. 2002). Also tyrosine kinases regulate many inflammatory modulators that regulate immune response (Ingley 2012; Manning et al. 2002). Src family kinases (SFKs) include different tyrosine kinases like Src, Lyn, Yes, Fyn, Blk, Yrk, Fgr, Hck, and Lck. These intracellular membrane-associated non-receptor tyrosine kinases control different biological processes (Ingley et al. 2007; Parsons and Parsons 2004). The overexpression and higher activity of SFKs enhance different types of cancer cell growth, and various studies demonstrated the involvement of SFKs in various tumor progression and metastasis (Resh 1999; Boggon and Eck 2004; Selvakumar et al. 2007). Lyn is a member of the SFK family; solid tumors including colon cancer, prostate cancer,...

This is a preview of subscription content, log in to check access.

References

  1. Bates RC, Edwards NS, Burns GF, Fisher DE. A CD44 survival pathway triggers chemoresistance via lyn kinase and phosphoinositide 3-kinase/Akt in colon carcinoma cells. Cancer Res. 2001;61:5275–83.PubMedGoogle Scholar
  2. Boggon TJ, Eck MJ. Structure and regulation of Src family kinases. Oncogene. 2004;23:7918–27.CrossRefPubMedGoogle Scholar
  3. Choi YL, Bocanegra M, Kwon MJ, Shin YK, Nam SJ, Yang JH, et al. LYN is a mediator of epithelial-mesenchymal transition and a target of dasatinib in breast cancer. Cancer Res. 2010;70:2296–306.PubMedPubMedCentralCrossRefGoogle Scholar
  4. Contri A, Brunati AM, Trentin L, Cabrelle A, Miorin M, Cesaro L, et al. Chronic lymphocytic leukemia B cells contain anomalous Lyn tyrosine kinase, a putative contribution to defective apoptosis. J Clin Invest. 2005;115:369–78.PubMedPubMedCentralCrossRefGoogle Scholar
  5. Croucher DR, Hochgräfe F, Zhang L, Liu L, Lyons RJ, Rickwood D, et al. Involvement of Lyn and the atypical kinase SgK269/PEAK1 in a basal breast cancer signaling pathway. Cancer Res. 2013;73:1969–80.CrossRefPubMedGoogle Scholar
  6. Ding Q, Stewart J, Olman MA, Klobe MR, Gladson CL. The pattern of enhancement of Src kinase activity on platelet-derived growth factor stimulation of glioblastoma cells is affected by the integrin engaged. J Biol Chem. 2003;278:39882–91.CrossRefPubMedGoogle Scholar
  7. Donato NJ, Wu JY, Stapley J, Gallick G, Lin H, Arlinghaus R, et al. BCR-ABL independence and LYN kinase overexpression in chronic myelogenous leukemia cells selected for resistance to STI571. Blood. 2003;101:690–8.CrossRefPubMedGoogle Scholar
  8. Dong S, Byrd JC. A new role for Lyn in the CLL microenvironment. Cancer Cell. 2016;30:511–2.CrossRefPubMedGoogle Scholar
  9. Dos Santos C, Demur C, Bardet V, Prade-Houdellier N, Payrastre B, Recher C. A critical role for Lyn in acute myeloid leukemia. Blood. 2008;111:2269–79.CrossRefPubMedGoogle Scholar
  10. Finn RS, Dering J, Ginther C, Wilson CA, Glaspy P, Tchekmedyian N, et al. Dasatinib, an orally active small molecule inhibitor of both the src and abl kinases, selectively inhibits growth of basal-type/“triple-negative” breast cancer cell lines growing in vitro. Breast Cancer Res Treat. 2007;105:319–26.CrossRefPubMedGoogle Scholar
  11. Futami M, Zhu QS, Whichard ZL, Xia L, Ke Y, Neel BG, et al. G-CSF receptor activation of the Src kinase Lyn is mediated by Gab2 recruitment of the Shp2 phosphatase. Blood. 2011;118:1077–86.PubMedPubMedCentralCrossRefGoogle Scholar
  12. Guan H, Zhou Z, Gallick GE, Jia SF, Morales J, Sood AK, et al. Targeting Lyn inhibits tumor growth and metastasis in Ewing’s sarcoma. Mol Cancer Ther. 2008;7:1807–16.PubMedPubMedCentralCrossRefGoogle Scholar
  13. Hibbs ML, Stanley E, Maglitto R, Dunn A. Identification of a duplication of the mouse Lyn gene. Gene. 1995;156:175–81.CrossRefPubMedGoogle Scholar
  14. Hu YG, Liu YH, Pelletier S, Buchdunger E, Warmuth M, Fabbro D, et al. Requirement of Src kinases Lyn, Hck and Fgr for BCR-ABL1-induced B-lymphoblastic leukemia but not chronic myeloid leukemia. Nat Genet. 2004;36:453–61.CrossRefPubMedGoogle Scholar
  15. Huang F, Reeves K, Han X, Fairchild C, Platero S, Wong TW, et al. Identification of candidate molecular markers predicting sensitivity in solid tumors to dasatinib: rationale for patient selection. Cancer Res. 2007;67:2226–38.CrossRefPubMedGoogle Scholar
  16. Huang TH, Huo L, Wang YN, Xia W, Wei Y, Chang SS, et al. Epidermal growth factor receptor potentiates MCM7-mediated DNA replication through tyrosine phosphorylation of Lyn kinase in human cancers. Cancer Cell. 2013;23:796–810.PubMedPubMedCentralCrossRefGoogle Scholar
  17. Ingley E. Functions of the Lyn tyrosine kinase in health and disease. Cell Commun Signal. 2012;10:21.PubMedPubMedCentralCrossRefGoogle Scholar
  18. Ingley E, Payne CJ, Murphy SV, McCarthy DJ, Schnieder JR, Rossjohn J, et al. Src Family Kinases: regulating their activity, levels and identifying new pathways. Acta Biochim Pol. 2007;54:9–10.Google Scholar
  19. Koch C, Anderson D, Moran M, Ellis C, Pawson T. SH2 and SH3 domains: elements that control interactions of cytoplasmic signalling proteins. Science. 1991;252:668–74.CrossRefPubMedGoogle Scholar
  20. Lida M, Brand TM, Campbell DA, Li C, Wheeler DL. Yes and Lyn play a role in nuclear translocation of the epidermal growth factor receptor. Oncogene. 2013;32:759–67.CrossRefGoogle Scholar
  21. Liu WM, Huang P, Kar N, Burgett M, Muller-Greven G, Nowacki AS, et al. Lyn facilitates glioblastoma cell survival under conditions of nutrient deprivation by promoting autophagy. PLoS One. 2013;8:e70804.PubMedPubMedCentralCrossRefGoogle Scholar
  22. Lriyama N, Yuan B, Hatta Y, Takagi N, Takei M. Lyn, a tyrosine kinase closely linked to the differentiation status of primary acute myeloid leukemia blasts, associates with negative regulation of all-trans retinoic acid (ATRA) and dihydroxyvitamin D3 (VD3)-induced HL-60 cells differentiation. Cancer Cell Int. 2016;16:37.CrossRefGoogle Scholar
  23. Manning G, Whyte D, Martinez R, Hunter T, Sudarsanam S. The protein kinase complement of the human genome. Science. 2002;298:1912–34.PubMedCrossRefGoogle Scholar
  24. Meyn MA, Wilson MB, Abdi FA, Fahey N, Schiavone AP, Wu J, et al. Src family kinases phosphorylate the Bcr-Abl SH3-SH2 region and modulate Bcr-Abl transforming activity. J Biol Chem. 2006;281:30907–16.CrossRefPubMedGoogle Scholar
  25. Nguyen PH, Fedorchenko O, Rosen N, Koch M, Barthel R, Winarski T, et al. LYN kinase in the tumor microenvironment is essential for the progression of chronic lymphocytic leukemia. Cancer Cell. 2016;30:610–22.CrossRefPubMedGoogle Scholar
  26. Park SI, Zhang J, Phillips KA, Araujo JC, Najjar AM, Volgin AY, et al. Targeting SRC family kinases inhibits growth and lymph node metastases of prostate cancer in an orthotopic nude mouse model. Cancer Res. 2008;68:3323–33.CrossRefPubMedGoogle Scholar
  27. Parsons SJ, Parsons JT. Src family kinases, key regulators of signal transduction. Oncogene. 2004;23:7906–9.CrossRefPubMedGoogle Scholar
  28. Pendergast AM, Quilliam LA, Cripe LD, Bassing CH, Dai Z, Li N, et al. BCR-ABL-induced oncogenesis is mediated by direct interaction with the SH2 domain of the GRB-2 adaptor protein. Cell. 1993;75:175–85.CrossRefGoogle Scholar
  29. Pénzes K, Baumann C, Szabadkai I, Orfi L, Kéri G, Ullrich A, et al. Combined inhibition of AXL, Lyn and p130Cas kinases block migration of triple negative breast cancer cells. Cancer Biol Ther. 2014;15:1571–82.PubMedPubMedCentralCrossRefGoogle Scholar
  30. Resh MD. Fatty acylation of proteins: new insights into membrane targeting of myristoylated and palmitoylated proteins. Biochim Biophys Acta. 1999;1451:1–16.CrossRefPubMedGoogle Scholar
  31. Roginskaya V, Zuo S, Caudell E, Nambudiri G, Kraker AJ, Corey SJ. Therapeutic targeting of Src-kinase Lyn in myeloid leukemic cell growth. Leukemia. 1999;13:855–61.CrossRefPubMedGoogle Scholar
  32. Saini S, Majid S, Shahryari V, Tabatabai ZL, Arora S, Yamamura S, et al. Regulation of SRC kinases by microRNA-3607 located in a frequently deleted locus in prostate cancer. Mol Cancer Ther. 2014;13:1952–63.PubMedPubMedCentralCrossRefGoogle Scholar
  33. Samanta AK, Chakraborty SN, Wang Y, Kantarjian H, Sun X, Hood J, et al. Jak2 inhibition deactivates Lyn kinase through the SET-PP2A-SHP1 pathway, causing apoptosis in drug-resistant cells from chronic myelogenous leukemia patients. Oncogene. 2009;28:1669–81.PubMedPubMedCentralCrossRefGoogle Scholar
  34. Schwarz LJ, Fox EM, Balko JM, Garrett JT, Kuba MG, Estrada MV, et al. LYN-activating mutations mediate antiestrogen resistance in estrogen receptor-positive breast cancer. J Clin Invest. 2014;124:5490–502.PubMedPubMedCentralCrossRefGoogle Scholar
  35. Selvakumar P, Lakshmikuttyamma A, Shrivastav A, Das SB, Dimmock JR, Sharma RK. Potential role of N-myristoyltransferase in cancer. Prog Lipid Res. 2007;46:1–36.CrossRefPubMedGoogle Scholar
  36. Stettner MR, Wang W, Nabors LB, Bharara S, Flynn DC, Grammer JR, Gillespie GY, Gladson CL. Lyn kinase activity is the predominant cellular SRC kinase activity in glioblastoma tumor cells. Cancer Res. 2005;65:5535–43.PubMedPubMedCentralCrossRefGoogle Scholar
  37. Sun G, Sharma AK, Budde RJ. Autophosphorylation of Src and yes blocks their inactivation by Csk phosphorylation. Oncogene. 1998;17:1587–95.PubMedPubMedCentralCrossRefGoogle Scholar
  38. Sun G, Ramdas L, Wang W, Vinci J, McMurray J, Budde RJ. Effect of autophosphorylation on the catalytic and regulatory properties of protein tyrosine kinase Src. Arch Biochem Biophys. 2002;397:11–7.PubMedPubMedCentralCrossRefGoogle Scholar
  39. Sutton P, Borgia JA, Bonomi P, Plate JM. Lyn, a Src family kinase, regulates activation of epidermal growth factor receptors in lung adenocarcinoma cells. Mol Cancer. 2013;12:76.PubMedPubMedCentralCrossRefGoogle Scholar
  40. Tabariès S, Annis MG, Hsu BE, Tam CE, Savage P, Park M, et al. Lyn modulates Claudin-2 expression and is a therapeutic target for breast cancer liver metastasis. Oncotarget. 2015;6:9476–87.PubMedPubMedCentralCrossRefGoogle Scholar
  41. Takeda Y, Nakaseko C, Tanaka H, Takeuchi M, Yui M, Saraya A, et al. Direct activation of STAT5 by ETV6-LYN fusion protein promotes induction of myeloproliferative neoplasm with myelofibrosis. Br J Haematol. 2011;153:589–98.PubMedPubMedCentralCrossRefGoogle Scholar
  42. Tauzin S, Ding H, Khatib K, Ahmad I, Burdevet D, van Echten-Deckert G, et al. Oncogenic association of the Cbp/PAG adaptor protein with the Lyn tyrosine kinase in human B-NHL rafts. Blood. 2008;111:2310–20.PubMedPubMedCentralCrossRefGoogle Scholar
  43. Wang D, Esselman WJ, Cole PA. Substrate conformational restriction and CD45-catalysed dephosphorylation of tail tyrosine-phosphorylated Src protein. J Biol Chem. 2002;277:40428–33.PubMedPubMedCentralCrossRefGoogle Scholar
  44. Warmuth M, Simon N, Mitina O, Mathes R, Fabbro D, Manley PW, et al. Dual-specific Src and Abl kinase inhibitors, PP1 and CGP76030, inhibit growth and survival of cells expressing imatinib mesylate-resistant Bcr-Abl kinases. Blood. 2003;101:664–72.PubMedPubMedCentralCrossRefGoogle Scholar
  45. Wilson MB, Schreiner SJ, Choi HJ, Kamens J, Smithgall TE. Selective pyrrolo-pyrimidine inhibitors reveal a necessary role for Src family kinases in Bcr-Abl signal transduction and oncogenesis. Oncogene. 2002;21:8075–88.PubMedPubMedCentralCrossRefGoogle Scholar
  46. Wu J, Meng F, Lu H, Kong L, Bornmann W, Peng Z, et al. Lyn regulates BCR-ABL and Gab2 tyrosine phosphorylation and c-Cbl protein stability in imatinib resistant chronic myelogenous leukemia cells. Blood. 2008;111:3821–9.PubMedPubMedCentralCrossRefGoogle Scholar
  47. Yi T, Bolen JB, Ihle JN. Hematopoietic cells express two forms of lyn kinase differing by 21 amino acids in the amino terminus. Mol Cell Biol. 1991;11:2391–8.PubMedPubMedCentralCrossRefGoogle Scholar
  48. Zardan A, Nip KM, Thaper D, Toren P, Vahid S, Beraldi E, et al. Lyn tyrosine kinase regulates androgen receptor expression and activity in castrate-resistant prostate cancer. Oncogenesies. 2014;3:e115.CrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  • Sai Kundur
    • 3
  • Hung Nguyen
    • 3
  • Lloyd McKee
    • 3
  • Clairissa Cruz
    • 3
  • Ponniah Selvakumar
    • 1
    • 2
    • 3
  • Ashakumary Lakshmikuttyamma
    • 3
  1. 1.Department of Pathology and Laboratory Medicine, College of MedicineUniversity of SaskatchewanSaskatoonCanada
  2. 2.Cancer Research Unit, Saskatchewan Cancer AgencySaskatoonCanada
  3. 3.Department of Pharmaceutical SciencesJefferson College of Pharmacy, Thomas Jefferson UniversityPhiladelphiaUSA