J. Thomas Parsons
- BA, Depauw University, Greencastle, IN
- Postdoc, St. Louis University, St Louis, MO
- PhD, Duke University, Durham, NC
- Postdoc, Universitat Zurich, Zurich, Switzerland
- Professor, Microbiology, Immunology, and Cancer Biology
- Phone: 434-924-5395
- Email: email@example.com
Adhesion Signaling in Normal, Cardiovascular and Cancer Cells
Protein Kinases in Cell Adhesion;The long term goal of our research is to understand how signal transduction cascades initiated by growth factors and extracellular matrix-integrin interactions regulate cell adhesion, cell motility, cell growth and differentiation. We seek to understand how such signaling pathways are organized (wired) in normal cells and to ultimately define the cellular alterations (both genetic and environmental) that lead to abnormal adhesion signaling in cancer cells. Studies over the past five years have identified two major classes of signaling molecules that participate in and regulate adhesion signaling, protein tyrosine kinases and members of the family of small GTPases. How these two classes of regulatory proteins function to organize the complex signaling required for cell adhesion and movement is a central theme of our laboratory. One area of intense study is the role of focal adhesion kinase (FAK) in mediating signals from the extracellular matrix through the beta-integrin receptors. We are focusing on the identification and characterization of molecules that directly interact with FAK and link FAK with both upstream and downstream signaling components. We are seeking to define the role of FAK and interacting partners in mediating signals that regulate cell motility and growth. Finally we are studying how cells utilize a potentially novel mechanism to regulate adhesion signaling during development. A second area of emphasis in the laboratory is to understand how individual tyrosine kinase substrates contribute to tyrosine kinase directed signaling. Studies of "cortactin", a tyrosine phosphorylated actin binding protein, point to a role for cortactin in the control of membrane ruffling and cell motility. Future studies will focus on the role of the cytoskeleton and associated regulatory proteins in orchestrating compartmentalized signaling in response to growth factor and adhesion signals during normal developmental processes and in cancer cells.
- Bernaciak T, Zareno J, Parsons J, Silva C. A novel role for signal transducer and activator of transcription 5b (STAT5b) in beta1-integrin-mediated human breast cancer cell migration. Breast Cancer Res. 11(4): R52. PMCID: PMC2750113
- Martin K, Jeffery E, Grigera P, Shabanowitz J, Hunt D, Parsons J. Cortactin phosphorylation sites mapped by mass spectrometry. J Cell Sci. 119 2851-3.
- Slack-Davis J, Martin K, Tilghman R, Iwanicki M, Ung E, Autry C, Luzzio M, Cooper B, Kath J, Roberts W, Parsons J. Cellular characterization of a novel focal adhesion kinase inhibitor. J Biol Chem. 282(20): 14845-52.
- Zhang X, Yuan Z, Zhang Y, Yong S, Salas-Burgos A, Koomen J, Olashaw N, Parsons J, Yang X, Dent S, Yao T, Lane W, Seto E. HDAC6 modulates cell motility by altering the acetylation level of cortactin. Mol Cell. 27(2): 197-213. PMCID: PMC2684874
- Hayasaka H, Martin K, Hershey E, Parsons J. Disruption of FRNK expression by gene targeting of the intronic promoter within the focal adhesion kinase gene. J Cell Biochem. 102(4): 947-54.
- Mayhew M, Jeffery E, Sherman N, Nelson K, Polefrone J, Pratt S, Shabanowitz J, Parsons J, Fox J, Hunt D, Horwitz A. Identification of phosphorylation sites in betaPIX and PAK1. J Cell Sci. 120 3911-8.
- Vomastek T, Iwanicki M, Schaeffer H, Tarcsafalvi A, Parsons J, Weber M. RACK1 targets the extracellular signal-regulated kinase/mitogen-activated protein kinase pathway to link integrin engagement with focal adhesion disassembly and cell motility. Mol Cell Biol. 27(23): 8296-305. PMCID: PMC2169169
- Owen K, Pixley F, Thomas K, Vicente-Manzanares M, Ray B, Horwitz A, Parsons J, Beggs H, Stanley E, Bouton A. Regulation of lamellipodial persistence, adhesion turnover, and motility in macrophages by focal adhesion kinase. J Cell Biol. 179(6): 1275-87. PMCID: PMC2140030
- Tilghman R, Parsons J. Focal adhesion kinase as a regulator of cell tension in the progression of cancer. Semin Cancer Biol. 2008;18(1): 45-52. PMCID: PMC2267763
- Parsons J, Slack-Davis J, Tilghman R, Roberts W. Focal adhesion kinase: targeting adhesion signaling pathways for therapeutic intervention. Clin Cancer Res. 2008;14(3): 627-32.
- Iwanicki M, Vomastek T, Tilghman R, Martin K, Banerjee J, Wedegaertner P, Parsons J. FAK, PDZ-RhoGEF and ROCKII cooperate to regulate adhesion movement and trailing-edge retraction in fibroblasts. J Cell Sci. 2008;121(6): 895-905.
- Vomastek T, Iwanicki M, Burack W, Tiwari D, Kumar D, Parsons J, Weber M, Nandicoori V. Extracellular signal-regulated kinase 2 (ERK2) phosphorylation sites and docking domain on the nuclear pore complex protein Tpr cooperatively regulate ERK2-Tpr interaction. Mol Cell Biol. 2008;28(22): 6954-66. PMCID: PMC2573295
- Sayers R, Sundberg-Smith L, Rojas M, Hayasaka H, Parsons J, Mack C, Taylor J. FRNK expression promotes smooth muscle cell maturation during vascular development and after vascular injury. Arterioscler Thromb Vasc Biol. 2008;28(12): 2115-22. PMCID: PMC2785047
- Slack-Davis J, Hershey E, Theodorescu D, Frierson H, Parsons J. Differential requirement for focal adhesion kinase signaling in cancer progression in the transgenic adenocarcinoma of mouse prostate model. Mol Cancer Ther. 8(8): 2470-7. PMCID: PMC2728172
- Petzold T, Orr A, Hahn C, Jhaveri K, Parsons J, Schwartz M. Focal adhesion kinase modulates activation of NF-kappaB by flow in endothelial cells. Am J Physiol Cell Physiol. 297(4): C814-22. PMCID: PMC2770750
- Parsons J, Horwitz A, Schwartz M. Cell adhesion: integrating cytoskeletal dynamics and cellular tension. Nat Rev Mol Cell Biol. 11(9): 633-43.
- Tilghman R, Cowan C, Mih J, Koryakina Y, Gioeli D, Slack-Davis J, Blackman B, Tschumperlin D, Parsons J. Matrix rigidity regulates cancer cell growth and cellular phenotype. PLoS One. 5(9): e12905. PMCID: PMC2944843
- Stokes J, Adair S, Slack-Davis J, Walters D, Tilghman R, Hershey E, Lowrey B, Thomas K, Bouton A, Hwang R, Stelow E, Parsons J, Bauer T. Inhibition of focal adhesion kinase by PF-562,271 inhibits the growth and metastasis of pancreatic cancer concomitant with altering the tumor microenvironment. Molecular cancer therapeutics. 2011;10(11): 2135-45. PMID: 21903606 | PMCID: PMC3213273
- Tilghman R, Blais E, Cowan C, Sherman N, Grigera P, Jeffery E, Fox J, Blackman B, Tschumperlin D, Papin J, Parsons J. Matrix rigidity regulates cancer cell growth by modulating cellular metabolism and protein synthesis. PloS one. 2012;7(5): e37231. PMID: 22623999 | PMCID: PMC3356407
- Grigera P, Ma L, Borgman C, Pinto A, Sherman N, Parsons J, Fox J. Mass spectrometric analysis identifies a cortactin-RCC2/TD60 interaction in mitotic cells. Journal of proteomics. 2012;75(7): 2153-9. PMID: 22282019 | PMCID: PMC3312979