Department of Biological Sciences : Faculty Research

Maria Diakonova

Assistant Professor
Research Assistant Professor, University of Michigan, Ann Arbor
Postdoctoral Research Fellow, European Molecular Biology Laboratory (EMBL), Heidelberg, Germany,
Ph.D. Institute of Cytology, Russian Academy of Sciences, St.-Petersburg, 1993

Research

My current research is focused on the mechanisms by which JAK2 tyrosine kinase causes changes in cellular functions. Because JAK proteins are utilized by many cytokines, including interferons, most interleukins, ciliary neurotrophic factor, leptin, growth hormone, leukemia inhibitory factor, oncostatin M, erythropoietin, and granulocyte macrophage colony stimulating factor, our results may have wide applicability to cancer and other human diseases, such as obesity, diseases of the immune system, and neurological diseases. Main field of our interest is JAK2-dependent regulation of the serine-threonine kinase PAK1, a kinase implicated in multiple cellular functions, including apoptosis, MAP kinase regulation, PI3-kinase regulation and regulation of the actin cytoskeleton (Project I). Recent data suggest that PAK1 is involved in breast cancer progression. The primary focus of my lab is to understand how prolactin, JAK2 and PAK1 participate in human breast cancer.

Another field of my interest is a link between receptor tyrosine kinase and the actin cytoskeleton (Project II). Eukaryotic cells depend on signaling to the actin assembly for establishing their asymmetrical shapes, intracellular transport and locomotion, processes essential for morphogenesis, wound healing, immune responses, and metastasis of cancer cells. Most if not all ligands that activate receptor tyrosine kinases and receptor associated tyrosine kinases initiate such signals. However, we know very little about the signaling pathways that link receptor tyrosine kinases to the actin cytoskeleton. My recent data show that the adapter protein SH2-Bß provides such a link. I found that SH2-Bß enhances cell motility and binds the small GTPase Rac, one of the major actin-regulating proteins. I showed that SH2-Bß bundles actin filaments in vitro and binds to an actin-binding protein VASP. I demonstrated that SH2-Bß stimulates actin-based motility in an in vitro reconstitution system as well as in vivo using Listeria motility as a primary system. Current project in my lab is focused on further understanding SH2-Bß– actin cytoskeleton interactions.

Publications

1. Freedlanskaya I.I., Galactionov K.I., Diakonova M.Y., Pinaev G.F. Microfilamin- a new cytoskeleton 53 kD protein. DAN USSR, 289(6), 1511-1513, 1986
2. Poljanskaya G.G., Diakonova M.Y. The influence of cultivation conditions on the karyotypic structure of a subline of rat kangaroo kidney cells. Tsitologia, 30(11), 1355-1363, 1988
3. Diakonova M.Y., Sorkin A.D., Nikolsky N.N., Effect of primaquine on endocytosis of receptors of epidermal growth factor in A431 cells. Tsitologia, 34(7), p.63-69, 1992
4. Diakonova M.Y., Sorkin A.D., Nikolsky N.N. Internalization of normal and mutant receptors of the platelet-derived growth factor. Tsitologia, 34(8), p.74-81, 1992
5. Clement B., Loreal O., Rescan P.-Y., Levavasseur F., Diakonova M., Rissel M.,Helgoualc'h A.,Guillouzo A. Cellular origin of the hepatic extracellular matrix. In: Molecular and Cell Biology of Liver Fibrogenesis. Grenner Eds.,Kluver,UK, 1992.
6. Diakonova M.Y., Nikolsky N.N., Immunocytochemical study of the spontaneous and ligand-induced endocytosis of EGF-R in A431 cells, Tsitologia, 36(6), 74-81, 1994
7. Diakonova M., B.Payrastre, A.van Velzen, W.J. Hage,P.van Bergen en Henegouwen, J.Boonstra, F.Cremers,B.Humbel. EGF induces rapid and transient association of PLC?1 with EGF-receptor and filamentous actin at membrane ruffles of A431 cells. Journal of Cell Science, 108, 2499-2509, 1995
8. Medvedeva N., Chupreta S., Diakonova M., Tvorogov D., Blagovestschenskaia A., Nikolsky N. Action of nocodazol on redistribution of PLC1 under mitogenic signal. Tsitologia, 39, 872-878, 1997
9. Diakonova M., Chilov D., Arnautov A., Alexseyev V., Nikolsky N., Medvedeva N, Intracellular distribution of PLCgamma1 in cell lines with different level of transformation. Europ. J. Cell. Biol., 73, 360-367, 1997
10. Diakonova M., Gerke V., Ernst J., Liautard J.-P., van der Vusse,G., Griffiths G. Localization of five annexins in J774macrophages and on isolated phagosomes. Journal of Cell Science, 110, 1199-1213, 1997
11. Defacque H., M. Egeberg, A. Huberman, M. Diakonova, C. Roy, P. Mangeat, W. Voelter, G. Marriott, J. Pfannsteil, H. Faulstich, G. Griffiths. Involvement of ezrin/moesin in de novo actin assembly on phagosomal membranes. The EMBO J., 19, 199-212, 2000.
12. Diakonova M., J. Herrington, L. Rui, D. Gunter, C. Carter-Su. SH2-Bß is required for growth hormone-induced actin reorganization. J. Biological Chemistry, 275, 13126-13133, 2000.
13. Carter-Su C., L. Rui, J. Herrington, M. Stofega, M. Diakonova. Growth hormone signaling pathways. In "Targets for Growth Hormone and IGF-1 action", Ed R. Bouillon, 1-13, BioScientifica Ltd, Bristol, 2001.
14. Diakonova M., G. Bokoch, J.A. Swanson. Dynamics of cytockeletal proteins during Fcgamma-receptor-mediated phagocytosis in macrophages - Mol. Biol. of Cell, 13, 402-411, 2002.
15. Diakonova M., D. R. Gunter, J. Herrington, C.Carter-Su. SH2-Bß is a Rac binding protein that regulates cell motility - J. Biol. Chem., 277, 10669-10677, 2002.
16. O'Brien K.B., L.S. Argetsinger, M. Diakonova, and C.Carter-Su. YXXL motifs in SH2-Bß are phosphorylated by JAK2, JAK1, and platelet-derived growth factor receptor are required for membrane ruffling - J. Biol. Chem., 278, 11970-11978, 2003.
17. Gaddameedi R. R., M. J. Pushpanathan, R. F. Ransom, L. B. Holzman, F. C. Brosius III, M. Diakonova, P. Mathieson, M. A. Saleem, E. O. List, J. J. Kopchick, S. J. Frank, and R. K. Menon . Identification of the glomerular podocyte as a target for growth hormone action. Endocrinology, 148, 2045-2055, 2007.
18. Diakonova M., E. Helfer, S. Seveau, J. Swanson, C. Kocks, L. Rui, M.-F. Carlier, C. Carter-Su. Adapter Protein SH2-Bbeta Stimulates Actin-based Motility of Listeria monocytogenes in a VASP-dependent Fashion. Infection and Immunity, 75, 3581-3593, 2007.
19. Rider, L., A. Shatrova, E. P. Feener, L. Webb and M. Diakonova. JAK2 Tyrosine Kinase Phosphorylates PAK1 and Regulates PAK1 Activity and Functions – J. Biol. Chem., 282, 30985-30996, 2007.