Ulrike M. Lorenz, PhD
Graduate School: Free University of Berlin, Germany
Primary Appointment: Associate Professor, Microbiology, Immunology, and Cancer Biology
Involvement of the protein tyrosine phosphatase SHP-1 in signal transduction pathways
Email Address: email@example.com
Tyrosyl phosphorylation and dephosphorylation of proteins are a key regulatory mechanism in many normal signal transduction pathways leading to cell proliferation, differentiation, and death. The steady state level of tyrosyl phosphorylation on any protein is determined by the opposing actions of protein tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPs). While a lot is known about the structure and functions of PTKs, relatively little is known about the details of PTPs' participation in signal transduction. My research interest focuses on the involvement of the PTP SHP-1 in the above described processes. SHP-1 is a non-transmembrane, src homology 2 (SH2)-domain containing PTP expressed primarily in hematopoietic cells of all lineages and at lower levels in epithelial cells. In hematopoietic cells, SHP-1 has been found to be a negative regulator of a variety of receptors. Mutations in the SHP1 gene have been shown to cause the motheaten (me/me) phenotype. Mice homozygous for the me allele display a panoply of hematopoietic disorders resulting in death two to three weeks after birth.
The research presently ongoing in my lab can be divided into two major projects: (a) the role of SHP-1 in T cell development and function and (b) the role of SHP-1 in the development of breast tumors. In order to address the question how SHP1 is involved in various signal transduction pathways, my laboratory employs techniques of protein chemistry, molecular biology and cell biology along with genetic approaches using me/me mice. Our goal is to understand the biological function(s) of SHP1 and their underlying mechanism(s) using a combination of in vitro and in vivo approaches.
Mauldin IS, Tung KS, Lorenz UM. The tyrosine phosphatase SHP-1 dampens murine Th17 development. Blood. 2012 May 10;119(19):4419-29. doi: 10.1182/blood-2011-09-377069. Epub 2012 Mar 20.
Lorenz U. Protein tyrosine phosphatase assays. Curr Protoc Immunol. 2011 Apr;Chapter 11:Unit 11.7. doi: 10.1002/0471142735.im1107s93.
Iype T, Sankarshanan M, Mauldin IS, Mullins DW, Lorenz U. The protein tyrosine phosphatase SHP-1 modulates the suppressive activity of regulatory T cells. J Immunol. 2010 Nov 15;185(10):6115-27. doi: 10.4049/jimmunol.1000622. Epub 2010 Oct 15.
Lorenz U. SHP-1 and SHP-2 in T cells: two phosphatases functioning at many levels. Immunol Rev. 2009 Mar;228(1):342-59. doi: 10.1111/j.1600-065X.2008.00760.x. Review.
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