Jolinda A. Traugh
Professor of Biochemistry and Director of the MARC U* Minority Undergraduate Training Program

Signal Transduction Molecular Biology Ph.D., University of California, Los Angeles, 1970 Resident Scholar, Rockefeller Foundation Conference and Study Center, Belliago, Italy, 1979 Biochemistry Study Section, National Institutes of Health, 1976-1980 Board of Scientific Counselors, National Institute of Environmental Health Sciences, 1985-1989; Chair, 1987-1989 Advisory Panel, Molecular Biochemistry Program, National Science Foundation, 1994-1997 Fellow, American Association for Advancement of Science, 1996 Editorial Board, Journal of Biological Chemistry, 2000-2005 VOICE: 951-827-4239 MAIL: jolinda.traugh@ucr.edu

 

Research Interest

 

Protein phosphorylation is a key element in the regulation of cell growth, cell stasis and cell death.  Research in my laboratory is focused on the protein kinase Pak2, which is involved in regulation of the onset of cytostasis and in apoptosis. Pak2 is activated in response to moderate stress by binding of Cdc42(GTP) followed by autophosphorylation.  In response to apoptotic stress, Pak2 is cleaved by caspase 3 then activated by autophosphorylation.  In contrast, Pak2 is inactive in dividing cells.

 

Pak2 is a 58 kDa protein with an amino-terminal regulatory domain and a carboxy-terminal catalytic domain.  Eight autophosphorylation sites have been identified by microsequence analysis and manual Edman degradation.  Seven phosphoserines are present in the regulatory domain and one phosphothreonine in the catalytic domain; the latter (Thr402) is required for activation.

 

Pak2 is activated in response to ionizing radiation, DNA-damaging drugs, hyperosmolarity and serum starvation.  Moderate stress results in the translocation and targeting of the protein kinase to the endoplasmic reticulum, where it becomes activated.  Using site-directed mutations, we have identified sites involved in the translocation of Pak2 and regulation of the cytostatic response.

 

A number of key regulatory proteins phosphorylated by Pak2 are involved in the cytostatic response.  These include proteins involved in cell division such as histones, the transcription factor c-Myc, translation mutation factors including eIF4G, and other protein kinases including cAbl.  Current studies examine the functional regulation of Pak2 and analysis of the Pak2 structure by hydrogen/deuterium exchange.  A second focus is the identification and regulation of substrates by Pak2 and determination of their role in the induction of cytostasis and inhibition of cell division.

 

 

Selected Publications

 

Ling, J., Morely, S.J. and Traugh, J.A. Inhibition of Cap-dependent translation via phosphorylation of eIF4G by protein kinase Pak2, The EMBO Journal 24, 4094-4105 (2005).

 

Jung, J.-H., and Traugh, J.A. Regulation of the interaction of Pak2 with Cdc42 via autophosphorylation of serine 141. J Biol Chem, 280, 40025-40031 (2005).

Miah, S.M., Sada, K., Tuazon, P.T., Ling, J., Maeno, K., Kyo, S. Qu, X., Tohyama, Y., Traugh, J.A. and Yamamura, H. Activation of Syk protein-tyrosine kinase in response to osmotic stress requires interaction with p21-activated protein kinase Pak2/ g -PAK. Mol Cell Biol , 24, 71-83 (2004).

Huang, Z., Traugh, J.A. and Bishop, J.M. Negative control of the Myc protein by the stress-responsive kinase Pak2. Mol Cell Biol , 24, 1582-1504 (2004).

Orton, K.C., Ling, J., Waskiewicz, A.J., Cooper, J.A., Merrick , W.C., Korneeva, N.L. Rhoads, R.E., Sonenberg, N, and Traugh, J.A. Phosphorylation of Mnk1 by Caspase-activated Pak2/ g -PAK inhibits Phosphorylation and Interaction of eIF4G with Mnk. J. Biol. Chem . 279, 38649-38657 (2004).

Huang, Z. and Traugh, J.A. Localization of p21-activated protein kinase g -PAK/Pak2 in the endoplasmic reticulum is required for induction of cytostasis. J. Biol. Chem. 278, 13101-13109 (2003).

Tuazon, P.T., Lorenson, M.Y., Walker , A. M. and Traugh, J.A. p21-activated protein kinase g -PAK in pituitary secretory granules phosphorylates prolactin. FEBS Lett . 515, 84-88 (2002).

Roig, J. and Traugh, J.A. Cytostatic p21 G protein-activated protein kinase gamma-PAK, in Vitamins and Hormones (Ed. G. Litwack), Vol. 62, pp. 167-98, Academic Press, San Diego, CA (2001).

Traugh, J.A. Insulin, phorbol ester and serum regulate the elongation phase of protein synthesis, in Prog. Mol. Subcell. Biol. (Ed. R. E. Rhoads), Vol. 62, pp. 33-48, Springer-Verlag , Berlin (2001).

Roig, J., Tauzon, P.T., and Traugh, J.A. Cdc42-independent activation and translocation of the cytostatic p21-activated protein kinase gamma-PAK by sphingosine. FEBS Lett. 507, 195-199 (2001).

Roig, J., Tuazon, P.T., Zipfel, P.A., Pendergast, A.M., and Traugh, J.A. Functional interaction between c-Abl and the p21-activated protein kinase gamma-PAK. PNAS U.S.A. 97, 14346-14351 (2000).

Roig, J., Huang, Z., Lytle, C. and Traugh, J. A. p21-activated protein kinase gamma-PAK is translocated and activated in response to hyperosmolarity. J. Biol. Chem. 275 16933-16940, (2000).