Fosfatasas de tirosina en el sistema inmune
  
Andrés Alonso
T-cell Receptor; Fcg Receptor; Tyrosine phosphatases, Tyrosine kinases, VHR
Phone: +34-983-184-839 (Office)
Phone: +34-983-184-838 (Lab)

Reversible protein tyrosine phosphorylation is a key mechanism that regulates the vast majority of cellular processes, from gene expression to cell cycle, and is controlled by two types of enzymes with opposing actions, kinases and phosphatases. Although during the last decades there has been a great advance in the knowledge of kinases, phosphatases are much less known. In this sense, recently it has described that the human genome contains 107 tyrosine phosphatases, a few of them are not characterized yet. Our lab is interested in studying the function played by phosphatases in the immune response against pathogens.

Antigen binding to TCR (T-cell receptor), BCR (B-cell receptor) and FcR (Fc receptor) receptors in the immune cells activates signalling pathways that are initiated by phosphorylation of proteins on tyrosine residues. Disruption of normal protein phosphorylation levels in the proteins that participate in those signalling pathways may lead to diverse pathologies, such as autoimmune diseases or immunodeficiencies, either by increase or reduction of cell stimulation, respectively. In summary, on one hand we would like to determine the proteins that are phosphorylated on tyrosine in the immune cells activated by antigens, and on the other hand to determine the phosphatases that are involved in their regulation and mainly which is the physiological function of these phosphatases in the immune system. In particular, our attention is focus in a group of tyrosine phosphatases called dual specificity phosphatases, among which we are studying the role that plays VHR (VH1 related) in T cells stimulated through the TCR.

RECENT PUBLICATIONS

  1. Alonso A, Burkhalter S, Sasin J, Tautz L, Bogetz J, Huynh H, Bremer MC, Holsinger LJ, Godzik A, & Mustelin T (2004) The minimal essential core of a cysteine-based protein-tyrosine phosphatase revealed by a novel 16-kDa VH1-like phosphatase, VHZ. J. Biol. Chem.279: 35768-35774.
  2. Alonso A, Sasin J, Bottini N, Friedberg I, Osterman A, Godzik A, Hunter T, Dixon J, & Mustelin T (2004) Protein tyrosine phosphatases in the human genome. Cell 117: 699-711.
  3. Alonso A, Narisawa S, Bogetz J, Tautz L, Hadzic R, Huynh H, Williams S, Gjorloff-Wingren A, Bremer MC, Holsinger LJ, Millan JL, & Mustelin T (2004) VHY, a novel myristoylated testis-restricted dual specificity protein phosphatase related to VHX. J. Biol. Chem. 279: 32586-32591.
  4. Alonso A, Bottini N, Bruckner S, Rahmouni S, Williams S, Schoenberger SP, & Mustelin T (2004) Lck dephosphorylation at Tyr-394 and inhibition of T cell antigen receptor signaling by Yersinia phosphatase YopH. J. Biol. Chem. 279: 4922-4928.
  5. Mustelin T, Rahmouni S, Bottini N, & Alonso A (2003) Role of protein tyrosine phosphatases in T cell activation. Immunol. Rev. 191: 139-147.
  6. Alonso A, Rahmouni S, Williams S, van Stipdonk M, Jaroszewski L, Godzik A, Abraham RT, Schoenberger SP, & Mustelin T (2003) Tyrosine phosphorylation of VHR phosphatase by ZAP-70. Nat. Immunol. 2003: 44-48.
  7. Alonso A, Merlo JJ, Na S, Kholod N, Jaroszewski L, Kharitonenkov A, Williams S, Godzik A, Posada JD, & Mustelin T (2002) Inhibition of T cell antigen receptor signaling by VHR-related MKPX (VHX), a new dual specificity phosphatase related to VH1 related (VHR). J. Biol. Chem. 277: 5524-5528.
  8. Alonso A, Saxena M, Williams S, & Mustelin T (2001) Inhibitory role for dual specificity phosphatase VHR in T cell antigen receptor and CD28-induced Erk and Jnk activation. J. Biol. Chem. 276: 4766-4771.
IBGM

Instituto De Biología Y Genética Molecular.
Calle Sanz y Forés, 3, 47003 Valladolid. Ver mapa