This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Stettner, M. R. Articles by Gladson, C. L. Search for Related Content PubMed PubMed Citation Articles by Stettner, M. R. Articles by Gladson, C. L.

Lyn Kinase Activity Is the Predominant Cellular Src Kinase Activity in Glioblastoma Tumor Cells

Departments of ¹ Pathology-Division of Neuropathology, ² Medicine-Hematology/Oncology-Biostatistics Division, ³ Neurology, ⁴ Cell Biology, and ⁵ Surgery-Division of Neurosurgery, University of Alabama at Birmingham, Birmingham, Alabama and ⁶ Department of Microbiology, West Virginia University, Morgantown, West Virginia

Requests for reprints: Candece L. Gladson, Department of Pathology-Division of Neuropathology, University of Alabama at Birmingham, LHRB 567, 701 South 19th Street, Birmingham, AL 35294-0007. Phone: 205-975-7847; Fax: 205-934-7346; E-mail: gladson{at}uab.edu.

Cellular Src activity modulates cell migration, proliferation, and differentiation, and recent reports suggest that individual members of the Src family may play specific roles in these processes. As we have found that Lyn, but not Fyn, activity promotes migration of glioblastoma cells in response to the cooperative signal generated by platelet-derived growth factor receptor ß and integrin _vß₃, we compared the activity and expression of Lyn and Fyn in glioblastoma (grade IV) tumor biopsy samples with that in anaplastic astrocytoma (grade III) tumors, nonneoplastic brain, and normal autopsy brain samples. Lyn kinase activity was significantly elevated in glioblastoma tumor samples. Notably, the Lyn kinase activity accounted for >90% of pan-Src kinase activity in glioblastoma samples but only 30% of pan-Src kinase activity in the other groups. The levels of phosphorylation of the autophosphorylation site were consistent with significantly higher Lyn activity in glioblastoma tumor tissue than nonneoplastic brain. Although the normalized levels of Lyn protein and the relative levels of Lyn message were significantly higher in glioblastoma samples than nonneoplastic brain, the normalized levels of Lyn protein did not correlate with Lyn activity in the glioblastoma samples. There was no significant difference in the normalized levels of c-Src and Fyn protein and message in the glioblastoma and nonneoplastic brain. Immunostaining revealed that Lyn is located primarily in the glioblastoma cells in the tumor biopsies. These data indicate that Lyn kinase activity is significantly elevated in glioblastoma tumors and suggest that it is the Lyn activity that promotes the malignant phenotype in these tumors.

This article has been cited by other articles:

				M. J. Wagner and J. R. Smiley Herpes Simplex Virus Requires VP11/12 To Induce Phosphorylation of the Activation Loop Tyrosine (Y394) of the Src Family Kinase Lck in T Lymphocytes J. Virol., December 1, 2009; 83(23): 12452 - 12461. [Abstract] [Full Text] [PDF]

				K. V. Lu, S. Zhu, A. Cvrljevic, T. T. Huang, S. Sarkaria, D. Ahkavan, J. Dang, E. B. Dinca, S. B. Plaisier, I. Oderberg, et al. Fyn and Src Are Effectors of Oncogenic Epidermal Growth Factor Receptor Signaling in Glioblastoma Patients Cancer Res., September 1, 2009; 69(17): 6889 - 6898. [Abstract] [Full Text] [PDF]

				B. C. McFarland, J. Stewart Jr., A. Hamza, R. Nordal, D. J. Davidson, J. Henkin, and C. L. Gladson Plasminogen Kringle 5 Induces Apoptosis of Brain Microvessel Endothelial Cells: Sensitization by Radiation and Requirement for GRP78 and LRP1 Cancer Res., July 1, 2009; 69(13): 5537 - 5545. [Abstract] [Full Text] [PDF]

				V. Milano, Y. Piao, T. LaFortune, and J. de Groot Dasatinib-induced autophagy is enhanced in combination with temozolomide in glioma Mol. Cancer Ther., February 1, 2009; 8(2): 394 - 406. [Abstract] [Full Text] [PDF]

				H. Guan, Z. Zhou, G. E. Gallick, S.-F. Jia, J. Morales, A. K. Sood, S. J. Corey, and E. S. Kleinerman Targeting Lyn inhibits tumor growth and metastasis in Ewing's sarcoma Mol. Cancer Ther., July 1, 2008; 7(7): 1807 - 1816. [Abstract] [Full Text] [PDF]

				C. E. Ducker, L. K. Griffel, R. A. Smith, S. N. Keller, Y. Zhuang, Z. Xia, J. D. Diller, and C. D. Smith Discovery and characterization of inhibitors of human palmitoyl acyltransferases. Mol. Cancer Ther., July 1, 2006; 5(7): 1647 - 1659. [Abstract] [Full Text] [PDF]