Alexander Y. Tsygankov, PhD
Associate Professor, Microbiology and Immunology
Associate Professor, Sol Sherry Thrombosis Research Center
Associate Professor, Fels Institute for Cancer Research and Molecular Biology
- Contact Information
- About Me
Dr. Tsygankov’s research interests lie in the area of cell signaling, in particular, of its regulation by protein tyrosine kinases and phosphatases. Previous work of this laboratory with protein kinases of Src and Syk families and adaptor proteins of Cbl family, which is involved in Src- and Syk-mediated signaling, defined the novel protein family TULA. Dr. Tsygankov’s laboratory identified and characterized TULA, a Cbl-associated protein and later demonstrated that TULA-2, but not TULA, is an active protein tyrosine phosphatase capable of dephosphorylating Syk, which along with the highly-related kinase Zap-70 is a bona-fide substrate of TULA-2.
The current interests of Dr. Tsygankov are focused on understanding the role of TULA-family proteins in cell signaling and activation. This issue is addressed in two experimental systems – T lymphocytes and platelets. The results of the laboratory indicate that TULA- and TULA-2-null mice are significantly more responsive to experimentally induced colitis and that this inflammation to a large degree depends on hyper-responsiveness of TULA-deficient T cells to stimulation through T-cell antigen receptor. These results are directly related to understanding of molecular and cellular mechanisms of inflammatory bowel disease.
In collaboration with platelet experts, including Dr. Kunapuli from Temple University School of Medicine, Dr. Tsygankov’s group has also shown that TULA-2-mediated dephosphorylation of Syk significantly reduces platelet signaling mediated by GPVI collagen receptor, thus increasing the platelet activation threshold, which prevents unnecessary and potentially dangerous stimulation of platelet responses by sub-optimal stimuli. These results indicate that TULA-2-null platelet exhibit greatly potentiated responses in vitro and in vivo. Likewise, pharmacological inhibition of TULA-2 by a novel compound appears to exert similar effects on platelets. The current focus of Dr. Tsygankov’s laboratory in these studies is deciphering the molecular mechanism of down-regulatory functions of TULA-2 in GPVI signaling and assessing the therapeutic potential of TULA-2 as a target in treatment of platelet-dependent bleeding disorders.
- Education, Training & Credentials
- Bach Institute of Biochemistry, Moscow
Teckchandani AM, Birukova AA, Tar K, Verin AD, Tsygankov AY, The multidomain protooncogenic protein c-Cbl binds to tubulin and stabilizes microtubules. Exp Cell Res 2005 May 15;306(1):114-27.
Dangelmaier CA, Quinter PG, Jin J, Tsygankov AY, Kunapuli SP, Daniel JL, Rapid ubiquitination of Syk following GPVI activation in platelets. Blood 2005 May 15;105(10):3918-24.
Raymond AD, Hasham MG, Tsygankov AY, Henderson EE, Herpesvirus saimiri-encoded proteins Tip and StpC modulate human immunodeficiency virus type 1 replication in T-cell lines and lymphocytes independently of viral tropism. Virology 2004 Jun 20;324(1):60-6.
Feshchenko EA, Smirnova EV, Swaminathan G, Teckchandani AM, Agrawal R, Band H, Zhang X, Annan RS, Carr SA, Tsygankov AY, TULA: an SH3- and UBA-containing protein that binds to c-Cbl and ubiquitin. Oncogene 2004 Jun 10;23(27):4690-706.
Sorokina EM, Merlo JJ Jr, Tsygankov AY, Molecular mechanisms of the effect of herpesvirus saimiri protein StpC on the signaling pathway leading to NF-kappaB activation. J Biol Chem 2004 279(14):13469-77.
Tsygankov AY, Teckchandani AM, Feshchenko EA, Swaminathan G, Beyond the RING: CBL proteins as multivalent adapters. Oncogene 2001 20(44):6382-402.
Merlo JJ, Tsygankov AY. Herpesvirus saimiri oncoproteins Tip and StpC synergistically stimulate NF-kappaB activity and interleukin-2 gene expression.
Virology. 2001 Jan 5;279(1):325-38.
Levkowitz G, Waterman H, Ettenberg SA, Katz M, Tsygankov AY, Alroy I, Lavi S, Iwai K, Reiss Y, Ciechanover A, Lipkowitz S, Yarden Y. Ubiquitin ligase activity and tyrosine phosphorylation underlie suppression of growth factor signaling by c-Cbl/Sli-1. Mol Cell. 1999 Dec;4(6):1029-40.
Feshchenko EA, Shore SK, Tsygankov AY. Tyrosine phosphorylation of C-Cbl facilitates adhesion and spreading while suppressing anchorage-independent growth of V-Abl-transformed NIH3T3 fibroblasts. Oncogene. 1999 Jun 24;18(25):3703-15.
Feshchenko EA, Langdon WY, Tsygankov AY. Fyn, Yes, and Syk phosphorylation sites in c-Cbl map to the same tyrosine residues that become phosphorylated in activated T cells. J Biol Chem. 1998 Apr 3;273(14):8323-31.
Tsygankov AY, Mahajan S, Fincke JE, Bolen JB. Specific association of tyrosine-phosphorylated c-Cbl with Fyn tyrosine kinase in T cells. J Biol Chem. 1996 Oct 25;271(43):27130-7.
Wiese N, Tsygankov AY, Klauenberg U, Bolen JB, Fleischer B, Broker BM. Selective activation of T cell kinase p56lck by Herpesvirus saimiri protein tip. J Biol Chem. 1996 Jan 12;271(2):847-52.
Biesinger B, Tsygankov AY, Fickenscher H, Emmrich F, Fleckenstein B, Bolen JB, Broker BM. The product of the Herpesvirus saimiri open reading frame 1 (tip) interacts with T cell-specific kinase p56lck in transformed cells. J Biol Chem. 1995 Mar 3;270(9):4729-34.
Tsygankov AY, Spana C, Rowley RB, Penhallow RC, Burkhardt AL, Bolen JB. Activation-dependent tyrosine phosphorylation of Fyn-associated proteins in T lymphocytes. J Biol Chem. 1994 Mar 11;269(10):7792-800.
Tsygankov AY, Broker BM, Fargnoli J, Ledbetter JA, Bolen JB. Activation of tyrosine kinase p60fyn following T cell antigen receptor cross-linking. J Biol Chem. 1992 Sep 15;267(26):18259-62. Collapse