Department of the Intracellular Signalling and Transport
    Неаd оf the Department

    NIKOLSKY Nikolay Nikolaevich

    Academician, Doctor of Biological Sciences, Professor

    Phone: +7 (812) 297-4596

The Department was founded in 2005th on the basis of the Laboratory of Cell Cycle Physiology and several research groups. Currently the area of the Department's scientific interests covers wide range of problems from regulatory mechanisms of signaling stimulated by receptor tyrosine kinases to some aspects of stem cells biology.

The work is conducted using cultivated mammal cells, including cultivated stem endometric human cells. Modern methods of biochemistry, molecular and cellular biology are used, confocal immunofluorescent microscopy and flow cytometry among them.

The studies are supported by grants of Russian Foundation for Basic Research, by Programs of RAS "Molecular and Cell Biology", by the President of Russian Federation grant for Science Schools, by Russian Agency for Science and Innovations, grants of the Government of Sankt-Petersburg, grants for Young Scientists, et al.

Structure of the Department:

The Department consists of several research groups, headed by Elena B. Burova, Galina F. Reshetnikova, Irina A. Gamaley and Irina I. Marakhova.

The Department includes:

Laboratory of Ionic Mechanisms of Cell Signaling (head - D.Sci., Ph.D. Yuri.A.Negulyaev)

Laboratory of Intracellular Membrane Dynamics (head - D.Sci., Ph.D., Prof. Elena S. Kornilova)

Group of Genetic Mechanisms of Cell Differentiation and Malignization (head - Ph.D. Tatiana M. Grinchuk)

Group of Flow Cytometry and Sorting (head - Ph.D. Valery V. Zenin)

Group of Cell Populations' Genetics (head - D.Sci., Ph.D., Prof. Vyacheslav M. Mikhaylov)

Main research interests of working group headed by Senior Scientist, Ph.D. Elena B. Burova (e-mail: are devoted to studying of intracellular signal transduction through the epidermal growth factor (EGF) receptor. The current interest is focused on the transactivation (ligand-independent activation) of the EGF receptor induced by interferon gamma and various oxidants. We have shown that in A431 cells overexpressing EGF receptor the extracellular signal transduction is characterized by a general pattern. Src/Jak2-dependent EGF receptor transactivation and ERK1/2 MAPK activation are involved in interferon gamma signaling. Metalloprotease-mediated HB-EGF release and Src-kinase regulate EGF receptor transactivation in A431 cells under oxidative stress. Furthermore, in these cells, H2O2-induced EGF receptor transactivation is essential for STAT1 and STAT3 activation.

Currently, we are investigating human endometrial stem cells (ESC). We are going to determine the resistance of ESC to various types of oxidative stress and to reveal the role of EGF receptor and other membrane-associated tyrosine kinases, as well as the involvement of signaling pathways Ras-MAPK, STAT, PI3K/Akt, Fas/FasL in the realization of ESC response to oxidative stress.

In addition, the investigation of EGF-induced death of A431 cells was carried out. The importance of the transcription factor STAT1 and p38 MAP kinase for EGF-dependent apoptosis of these cells was estimated. The mechanisms of downstream pro-apoptotic signaling from STAT1 and p38 are currently studied.

Mechanism of signal regulation by Hepatocyte Growth Factor (HGF) of c-Met receptor is investigated by the group headed by Ph.D. Galina F. Reshetnikova. c-Met is a member of the transmembrane receptor tyrosine kinase family and became activated upon HGF binding. c-Met regulates numerous physiological and pathological processes such as mammary tissue remodeling, wound healing, migration of myogenic precursor cells, liver regeneration, invasion and metastasis of tumor cells. Activation of c-Met also lead to weakening and subsequent destruction of cell-cell adhesion contact thereby increasing cell motility and invasion. However, particular signaling events which r egulate interplay between c-Met and intercellular adhesion remain obscure. Our group focuses on studies of influence of c-Met activation on the functional state of main intercellular adhesive protein E-cadherin.

The Group headed by Biological Sciences Doctor Irina A. Gamaley (e-mail: focuses its attention on molecular-physiological mechanisms of action of antioxidants (AO) on transformed, normal, and embryonic cells. Of particular interest is the ability of AO to decrease the susceptibility of transformed and embryonic cells to bacterial invasion and lytic activity of natural killer cells. The signal pathways underlying the effect are studied. They include effects of AO on cell morphology and cytoskeleton structures, on cell proliferation, on activity of matrix metalloproteinases. The methods applied include spectrometry, cytometry, zymography, Western blot analysis, confocal microscopy, etc. The Group has working connections with several laboratories of the Institute.

The main attention of the Group headed by Biological Sciences Doctor Irina I. Marakhova (e-mail: ) is focused on studying the mechanisms that are responsible for the expression of membrane-associated ion transporters during the initiation of cell proliferation and transformation. The most important conclusions are as follows: (1) the proliferation-related up-regulation of ion pump is due to an increased expression of Na/K-ATPase at the protein and the mRNA levels, and (2) signaling through both JAK/STAT and MAPK cascades is necessary to induce the interleukin-2-dependent functional and protein expression of the Na/K-ATPase in normal human lymphocytes. At present the signaling pathways involved in the expression of high-affinity receptor for interleukin-2 in human blood lymphocytes are under investigation

Main publications:

Voronkina I. V., K. M. Kirpichnikova, L. V. Smagina, I. V. Kozhucharova, and I. A. Gamaley. Dynamics of Matrix Metalloproteinases Activity of Primary Murine Embryonic Fibroblasts During Cultivation. Tsitologiya (Rus). 2011. 53 (1): 80-86.

Smirnova IS, Chang S, Forsthuber TG. 2010. Prosurvival and proapoptotic functions of ERK1/2 activation in murine thymocytes in vitro. Cell Immunol. 261(1):29-36.

Smirnova IS, Gonchar IV, Shatrova AN, Nikolsky NN, Burova EB. 2010. Metalloprotease-mediated HB-EGF release regulates EGF receptor transactivation in A431 cells under oxidative stress. Tsitologiya (Rus). 52(5):357-63.

Gamaley I. A., K. M. Kirpichnikova, E. A. Vakhromova, and N. A. Filatova. N-Acethylcysteine Reduces Susceptibility of Transformed and Embryonic Cells to Lytic Activity of Natural Killer Cells. Cell Tiss. Biol. 2010, 4 (6): 580-586.

Vakhromova E. A., Yu. S. Polozov, K. M. Kirpichnikova, N. D. Aksenov, and I. A. Gamaley. Effect of Alpha_Lipoic Acid on 3T3 and 3T3-SV40 Fibroblasts: Comparison with N-acetylcysteine. Cell Tiss. Biol. 2010, 4 (2): 185-191.

Karitskaya I., Aksenov N., Vassilieva I., Zenin V., Marakhova I. 2010. Long-term regulation of Na,K-ATPase pump during T-cell proliferation. Eur. J. Physiol. 460 : 777-789.

Voronkina I. V., K. M. Kirpichnikova, L. V. Smagina, and I. A. Gamaley. Activity of Matrix Metalloproteinases in Normal and Transformed Mouse Fibroblasts Exposed to Antioxidants. Cell Tiss. Biol. 2009, 3 (1): 56-60.

Filatova N.A., K.M. Kirpichnikova, E.A. Vahromova, I.A. Gamaley. Effect of Alpha-Lipoic Acid on the Sensitivity of Transformed Fibroblasts to Lysis by Natural Killer Cells. Comparison with NAC Action. Tsitologiya (Rus). 2009. 51 (5): 30-35.

Mikhelson V. M., I. A. Gamaley. Telomere shortening is a sole mechanism of aging. The Open Aging J. 2008. 2: 30-35.

Karitskaya I.A., Aksenov N.D., Vasiljeva I.O., Strelkova E.G., Marakhova I.I.2008. Long-term regulation of Na+/K+-ATPase pump in human lymphocytes: role of JAK/STAT and MAPK signaling pathways. Tsitologiya (Rus). 50 (4) : 329-337.

Gonchar IV, Dorosh VN, Nikolsky NN, Burova EB. 2008. The level of EGF receptor expression effects its transactivation by IFN gamma in epithelial cells. Tsitologiya (Rus). 50(10):887-92.

Filatova N. A., K. M. Kirpichnikova, I. A. Gamaley Reorganization of Acting Cytoskeleton in 3T3-SV40 Cells and Their Sensitivity to Lytic Activity of Natural Killer Cells. Cell Tiss. Biol. 2008, 2 (2): 146-152.

Bagaeva V.V., Avrov K.A., Reshetnikova G.F. 2007. Effect of E-cadherin on activation of MAP-kinase by growth factors in human carcinoma cells. Tsitologiya (Rus). 49(12):1017-1022.

Burova E, Vassilenko K, Dorosh V, Gonchar I, Nikolsky N. 2007. Interferon gamma-dependent transactivation of epidermal growth factor receptor. FEBS Lett. 581(7):1475-1480.

Reshetnikova G., Troyanovsky S., Rimm D. 2007. Definition of a direct interaction between Met and E-cadherin. Cell Biology International, 31:366-373.

Reshetnikova G. 2007. Met receptor subcellular localization depends on E-cadherin function. The Scientific World Journal. 7:2009-2011.

Grudinkin PS, Zenin VV, Kropotov AV, Dorosh VN, Nikolsky NN. 2007. EGF-induced apoptosis in A431 cells is dependent on STAT1, but not on STAT3. Eur. J. Cell. Biol. 86(10):591-603.

Vasilenko KP, Burova EB, Antonov VG, Nikolsky NN. 2006 Oxidized glutathione induces activation of the epidermal growth factor receptor and MAP kinases ERK 1,2. Tsitologiya (Rus). 48(6):500-507.

Smirnova IS, Aksenov ND, Kashuba EV, Payakurel P, Grabovetsky VV, Zaberezhny AD, Vonsky MS, Buchinska L, Biberfeld P, Hinkula J, Isaguliants MG. 2006. Hepatitis C virus core protein transforms murine fibroblasts by promoting genomic instability. Cell Oncol. 28(4):177-190.

Smirnova IS, Aksenov ND, Vonsky MS, Isaguliants MG. 2006. Different transformation pathways of murine fibroblast NIH 3T3 cells by hepatitis C virus core and NS3 proteins. Cell Biol Int. 30(11):915-919.

Karitskaya I.I., Aksenov N.D., Zenin V.V., Khaidukova A.L., Marakhova I.I. 2006. Activation of transcriptional factors STAT5 and STAT3 during initiation of human T-lymphocyte proliferation by various mitogenic agents. Tsitologiya (Rus). 48 (1) : 42-49.

Gamaley I., Efremova T., Kirpichnikova K., Kever L., Komissarchik Y., Polozov Yu., Khaitlina S. 2006. N-acetyl-cysteine-induced changes in susceptibility of transformed eukaryotic cells to bacterial invasion. Cell Biol. Int. 30 : 319-325.

Filatova N.A., Kirpichnikova K.M., Gamaley I.A. 2006. A decrease of activity of natural killers with respect to transformed fibroblasts 3Т3-SV40 treated with N-acetylcysteine. Tsitologiya (Rus), 48 (5) : 438-442.

Deev IE, Vasilenko KP, Kurmangaliev EZh, Serova OV, Popova NV, Galagan YS, Burova EB, Zozulya SA, Nikolsky NN, Petrenko AG. 2006. Effect of changes in ambient pH on phosphorylation of cellular proteins. Dokl Biochem Biophys (Rus).408:184-187.

Marakhova I.I., Karitskaya I.A., Aksenov N.D., Zenin V.V., Vinogradova T.A. 2005. Interleukin-2-dependent regulation of Na/K pump in human lymphocytes. FEBS Letters. 579 : 2773-2780.

Burova EB, Vasilenko KP, Antonov VG, Nikolsky NN. 2005. Transactivation of the epidermal growth factor receptor by oxidized glutathione and its pharmacological analogue Glutoxim in A431 cells. Dokl Biol Sci (Rus). 404:392-394.

Karitskaya I.I., Aksenov N.D., Vinogradova T.A., Marakhova I.I. 2005. Interleukin-2-regulated Na+,K+-ATPase expression level in activated human lymphocytes. Tsitologiya (Rus). 47 (1) : 28-37.

Efremova T.N., Kirpichnikova K.M., Khaitlina S.Yu., Gamaley I.A. 2004. Rearrangement of actin cytoskeleton in cells 3Т3 и 3Т3-SV40 in the presence of antioxidants. Tsitologiya (Rus). 46 (5): 395-403.

Vasilenko KP, Burova EB, Vinogradova NA, Nikolsky NN. 2004. Effect of nocodazole on the activation of transcription factors STAT1 and STAT3 in A431 cells. Tsitologiya. (Rus). 46(12):1025-1029.

Marakhova I.I., Vinogradova T.A., Karitskaya I.I., Epifantseva I.V., Aksenov N.D., Zenin V.V. 2004. Regulated expression of Na,K pump during human lymphocyte activation. Biol. Membr. (Rus). 21 (5) : 406-415.

Gamaley I.A., Aksenov N.D., Efremova T.N., Kirpichnikova K.M. 2003. Action of agents changing intracellular level of active oxygen forms on character of distribution of cells of lines 3T3 и 3T3SV40 in cell cycle phases. Tsitologiya. (Rus). 45 (1) : 21-28

Marakhova I.I., Aksenov N.D., Vinogradova T.A., Karitskaya I.I., Toropova F.V. 2003b. Change of Na-K-pump transport activity and binding of [3H[-labelled ouabain at various stages of human lymphocyte activation. Biol. Membr. (Rus). 20 (5) : 410-420.

Grudinkin PS, Bagaeva VV, Nikolsky NN. 2003. EGF-induced signal transduction in clonal cells of epidermoid carcinoma A431. Tsitologiya. (Rus). 45(2):158-165.

Burova EB, Gonchar IV, Nikolsky NN. 2003. STAT1 and STAT3 activation by oxidative stress in A431 cells involves Src-dependent EGF receptor transactivation. Tsitologiya. (Rus); 45(5):466-477.

Gonchar I.V, Burova E.B., Dorosh V.N., Gamaley I.A., Nikolsky N.N. 2003. Activation of EGF receptor and STAT factors depending on the oxidation-reduction status of cells A431. Tsitologiya. (Rus). 45 (5) : 478-487.

Marakhova I.I., Karitskaya I.I., Vinogradova T.A., Aksenov N.D., Moshkov A.V., Khaidukova A.L. 2003a. Change of sodium pump transport activity and Na+,K+-ATPase expression level in activated human lymphocytes. Tsitologiya. (Rus). 45 (11) : 1149-1157.

Svezhova N.V., Kirpichnikova K.M., Gamaley I.A. 2001. Interrelations of persisting oocysts of the protist cryptosporidium Cryptosporidium parvum with mouse resident peritoneal macrophages in vitro. Tsitologiya. (Rus). 43 (8) : 822-827.

Toropova F.V, Vinogradova T.A., Marakhova I.I. 2001. Comparative study of functional expression of Na/K pump in human lymphocytes activated by phytohemoagglutinin, phorbol ether, ionomycin, interleukin-2. Tsitologiya. (Rus). 43 (2) : 148-155.

Vasilenko KP, Butylin PA, Arnautov AM, Nikolsky NN. 2001. The role of SRC kinase in activation of transcription factor STAT1.Tsitologiya. (Rus). 43(11):1031-1037.

Vasilenko KP, Grudinkin PS, Arnautov AM, Burova EB, Nikolsky NN. 2001. Dynamics of the interaction of Stat1 transcription factor with the internalized EGF receptor and karyopherins alpha in response to stimulation of cells with epidermal growth factor. Tsitologiya. (Rus). 43(2):204-211.

Burova E.B., Grudinkin P.S., Bardin A.A., Gamaley I.A., Nikolsky N.N. 2001. H2O2-induced activation of transcriptional factors STAT1 and STAT3: role of RGF receptor and tyrosine kinase JAK2. Tsitologiya. (Rus). 43 (12) 1153-1161.

Burova EB, Grudinkin PS, Bardin AA, Gamaley IA, Nikolsky NN. 2001. H2O2-induced activation of transcription factors STAT1 and STAT3: the role of EGF receptor and tyrosine kinase JAK2.Tsitologiya. (Rus). 43(12):1153-1161.

Marakhova I.I., Vinogradova T.A., Toropova F.V. 2000. Na/K pump and cellular response to mitogenic signal. Biol. Memrany. (Rus). 17 (2) : 200-206.

Marakhova I.I., Vinogradova T.A., Toropova F.V. 2000. Na/K pump and cell response to mitogenic signal: regulatory mechanisms and relation to blast transformation. Membr. Cell Biol. 14 : 231-239.

Nikolsky NN, Vasilenko KP. 2000. STAT pathway of the intracellular signaling. Zh Evol Biokhim Fiziol. (Rus). 36(6):504-508.

Reshetnikova G., Barkan R., Popov B., Nikolsky N., Chang LS. 2000. Disruption of the actin cytoskeleton leads to inhibition of mitogen-induced cyclin E expression, Cdk2 phosphorylation, and nuclear accumulation of the retinoblastoma protein-related p107 protein. Exp. Cell Res., 259(1):35-53.

Marakhova I.I., Toropova F.V. 2000. Regulation of the Na,K-ATPase pump during cell cycle of activated human lymphocytes. Eur. Biophys. J. 29 : 328-329.

Klyubin I.V., Kirpichnikova K.M., Ischenko A.M., Zhakhov A.V., Gamaley I.A. 2000. The role of reactive oxygen species in membrane potential changes in macrophages and astrocytes. Membr. Cell Biol. 13 : 557-566.

Marakhova I.I., Ivanova A.E., Toropova F.V., Vereninov A.A., Vinogradova T.A. 1999. Functional expression of Na/K pump is controlled via a cyclosporin A-sensitive signalling pathway in activated human lymphocytes. FEBS Lett. 456 : 285-289.

Marakhova I.I., Vereninov A.A., Toropova F.V., Vinogradova T.A. 1998. Na,K-ATPase pump in activated human lymphocytes: on the mechanisms of rapid and long-term increase in K influxes during the initiation of phytohemagglutinin-induced proliferation. Biochim. Biophys. Acta. 1368 : 61-72.

Marakhova I.I., Vereninov A.A., Vinogradova T.A., Toropova F.V. 1998. Cyclosporin A inhibits long-term activation of Na,K pump in phytohemagglutinin-stimulated human lymphocytes. Membr. Cell Biol. 12 : 363-374.

Marakhova I.I., Vereninov A.A., Toropova F.V., Vinogradova T.A. 1996. Long-term enhancement of Na,K-ATPase pump during blasttransformation of human lymphocytes is controlled first by translational, then by transcriptional mechanisms. FEBS Lett. 368 : 110-112.

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