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Alfredo Fusco | Medical School of Naples - Itália

Grant number: 06/00359-5
Support Opportunities:Research Grants - Visiting Researcher Grant - International
Duration: July 29, 2006 - August 31, 2006
Field of knowledge:Biological Sciences - Biophysics - Molecular Biophysics
Principal Investigator:Igor Polikarpov
Grantee:Igor Polikarpov
Visiting researcher: Alfredo Fusco
Visiting researcher institution: Università degli Studi di Napoli Frederico II (UNINA), Italy
Host Institution: Instituto de Física de São Carlos (IFSC). Universidade de São Paulo (USP). São Carlos , SP, Brazil

Abstract

Phosphorylation of the tyrosines in proteins is a post-translational modification which is regulated by opposite action of two classes of proteins: proteins tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPs). Human PTPeta makes part of class I PTP and is composed by the extracelular part, containing eight fibronectine type III motives; one small transmembrane domain and an intracellular catalytic domain. Soon after its discovery, it was shown that PTPeta was able to inhibit growth of breast cancer cells; and subsequently group of Prof. Alfredo Fusco (Univ. Frederico II, Naples, Italy) demonstrated that rat PTPeta expression was down regulated in vitro in a thyroid tumor model and that its exogenous reconstitution in thyroid tumor cells was capable to block their proliferation via stabilization of the cell cycle inhibitor p27Kip1, as well as to directly inhibit colon, breast and lung tumors. Given a scientific importance of the protein tyrosine phosphatase eta for highly malignant thyroid tumor inhibition, present project aim at biophysical and structural studies of its intracellular catalytic domain. We plan to determine enzymatic activity of PTPeta and to characterize the protein by a combination of dynamic light scattering, native gel electrophoresis, circular dichroism, fluorescence spectroscopy and small angle X-ray scattering (SAXS), and to conduct its systematic crystallization studies. (AU)

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