THOMAS S. INGEBRITSEN, Associate Professor

Ph.D. Indiana University, 1979

e-mail: tsingebr@iastate.edu

TABLE OF CONTENTS

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Research Interests

My laboratory is interested in cellular signaling mechanisms with emphasis on protein phosphatases and their role the control of cell proliferation. Communication between cells of a multicellular organism is necessary for such vital functions as reproduction, growth and development, homeostatic control of physiological functions and adaptation to changes in the external environment. The most common mechanism of communication involves the release of signalling molecules (e.g. hormones, neurotransmitters, growth factors) from one cell type that interact with and activate specific receptor proteins on the surface of target cells. The activated receptor then generates an intracellular signal that ultimately couples to specific functional processes in cells to produce a physiological response. Studies of the signal transduction pathways that couple receptor activation to these physiological responses represent one of the most active and important research areas in modern biology.

The reversible attachment of phosphate to serine, threonine and tyrosine residues of cellular proteins is a control mechanism which plays a key role in most if not all signal transduction pathways. The extent of phosphorylation of a particular cell protein is controlled by two types of enzymes. Protein kinases add phosphate to the proteins while protein phosphatases remove the phosphate.

Currently my research is focusing on a protein tyrosine phosphatase termed PTP1B. Protein tyrosine phosphatases are a family of structurally related enzymes that remove phosphate from tyrosine residues of cell proteins. These enzymes are involved in regulating many cell processes including: cell proliferation, cell transformation, cell cycle, insulin action, platelet activation. We are addressing fundamental questions about how PTP1B recognizes its substrates. Since both the PTP1B and its substrates are proteins we want to know what features of substrate structure and correspondingly what features of PTP structure are important for substrate binding and reactivity. This project is important because it provides important information about the basis for substrate selection by PTP1B. Additionally the information could be helpful in the design of specific PTP antagonists which might have pharmaceutical applications. In another project we are trying to characterize two brain proteins that seem to function as specific inhibitors of PTP1B. Characterization of these inhibitors may provide new insights into the mechanisms for regulating PTP activity.

Selected References

Hippen, K.L., Jakes, S., Jena, B.P., Richards, J., Beck, B.L., Tabatabai, L.B. and Ingebritsen, T.S. (1993) Acidic residues are involved in substrate recognition by two soluble protein tyrosine phosphatases, PTP-5 and rrbPTP-1, Biochemistry 32, 12405-12412.

Ingebritsen, T.S., Hippin, K.L. and Hiriyanna, K.T. (1994) Protein phosphatases in cell proliferation, differentiation and development, in Growth Factors & Signal Transduction in Development (Nilsen-Hamilton, M., ed), Wiley-Liss, New York, pp. 139-163.

Hiriyanna, K.T., Baedke, D., Baek, K.H., Buck, B., Forney, B.A., Kordiyak, G. and Ingebritsen, T.S. (1994) Thiophosphorylated substrate analogs are potent active site-directed inhibitors of protein tyrosine phosphatases, Anal. Biochem. 223, 51-58.

Hiriyanna, K.T., Buck, B., Shen, S. and Ingebritsen, T.S. (1995) Thiophosphorylated RCM-lysozyme, an active site-directed protein tyrosine phosphatase inhibitor, inhibits the G2 to M transition during meiotic and mitotic cell cycles and uncouples MPF activation from the G2/M transition, Exp. Cell Res. 216, 21-29.

The active site of PTP1B

This diagram was drawn using the RasMol program.

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Public Education Program in Biotechnology

This program conducts educational activities with K-12 teachers, extension personnel and the community colleges. My current focus is the use of electronic networks to provide biotechnology education resources to high school teachers in the state of Iowa. I have developed a World Wide Web site for the Public Education Program in Biotechnology. The site has links to a wealth of biotechnology education information with emphasis at the high school level. Included are resources from Iowa State University (lab procedures, tips for teachers, the current and past issues of The Iowa Biotech Educator, The ISU Biotechnology Information Series, ISU biotechnology news releases), information on biotechnology products and their applications (animal products, plant products, food products, human health products and applications, regulatory information), and resources from other biotechnology programs (newsletters, listservers, Access Excellence). Some schools in Iowa are committed to using PSInet rather than the internet. Because of this we are also supplying many of the resources from the World Wide Web site to a Biotechnology section on PSInet.

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