Kathryn DeFea
Assistant Professor

Ph.D., University of California, San Francisco MAIL: katie.defea@ucr.edu

A number of receptors generate signals that converge at the activation of MAP Kinase (MAPK), yet they are still able to elicit specific downstream effects. Research in my lab is concerned with how different G-protein coupled receptors can utilize protein scaffolding complexes to direct the subcellular localization, and thus the downstream effects, of MAPK activation. We have purified two such complexes: one that is induced upon activation of Protease Activated Receptor 2 (PAR2), leading to cytoskeletal rearrangements and cell motility and another that forms in response to activation of Neurokinin-1 receptor (NK1R), leading to protection of cells from apoptosis. Current studies focus on biochemical dissection of these complexes, both by using proteomics to identify specific substrates and additional complex components, and using basic protein biochemistry to characterize molecular interactions between known components. We are also investigating the physiological consequences of formation of PAR2 and NK1R complexes, and the possibility that PAR2-induced cytoskeletal rearrangements play a role in tumor metastasis.

SELECTED PUBLICATIONS

Lan Ge, Youly Ly, Morley D. Hollenberg and Kathryn A. DeFea, Beta-arrestin-dependent sequestration of MAPK to pseudopodia is involved in PAR-2 mediated chemotaxis, J. Biol. Chem, 2003, 278 (36): 34418-26.

Tong Lin; Lingfang Zeng; Yi Liu; Kathryn DeFea; Martin A Schwartz; Shu Chien; John Y.-J.Shyy, Rho-ROCK-LIMK-Cofilin Pathway Regulates Shear Stress Activation of Sterol Regulatory Element Binding Proteins. Circulation Research, 2003, 92(12), 1296-1304.

K.A. DeFea, Z. Vaughn, E.M. O'Bryan, D. Nishijima, O. Dery and N.W. Bunnett. The Proliferative and Anti-Apoptotic Effects of Substance P are facilitated by Formation of a b-Arrestin Dependent Scaffolding Complex. Proc. Natl. Acad. Sci., U S A, 2000 26;97(20):11086-91.

K.A. DeFea, J. Zalevsky, M.S. Thoma, O. Dery, R.D. Mullins and N.W. Bunnett, b-Arrestin-Dependent Endocytosis of Proteinase-Activated Receptor-2 is Required for Intracellular Targeting of Activated ERK1/ 2. J. Cell Biology, 2000, 297 (2); 685-688.

Fabien Schmidlin, Olivier Dery, Kathryn DeFea, Lee Slice, Simona Patierno, Catia Sternini, Eileen F. Grady, and Nigel W. Bunnett, Dynamin and Rab5a dependent trafficking and signaling of the neurokinin-1 receptor J. Biol. Chem. 2001, 276(27):25427-25437.

Olivier Dery, Kathryn DeFea and Nigel W. Bunnett, Protein kinase C-mediated desensitization of the neurokinin 1 receptor. Am. J. Physiol. Cell Physiol. 2001, 280: C1097-C1106.

DeFea K, Schmidlin F, Dery O, Grady EF, Bunnett NW, Mechanisms of initiation and termination of signalling by neuropeptide receptors: a comparison with the proteinase-activated receptors. Biochem. Soc. Trans. 2000, Aug 1;28(4):419-426.

DeFea, K. and Roth, R.A. Modulation of Insulin Receptor Substrate-1 Tyrosine Phosphorylation and Function by Mitogen Activated Protein Kinase. J. Biological Chemistry, 1997, 272(50) 31400-31406.

DeFea, K. and Roth, R.A. Protein Kinase C Modulation of Insulin Receptor Substrate-1 Tyrosine Phosphorylation Requires Serine 612. Biochemistry 1997, 36 (42): 12939-12947.