Associate Professor, Biological Chemistry
Director, Graduate Program, Biological Chemistry
B.S., Pennsylvania. State University
Ph.D., Harvard University
Postdoctoral, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY
Postdoctoral, Fred Hutchinson Cancer Research Center, Seattle, WA
My laboratory studies proteins encoded by oncogenes. Our goal is to understand how these proteins work under normal physiological conditions and then to explore how their aberrant activation contributes to cancer formation and spread.
We study the proto-oncoprotein Ras and the signaling pathways that are activated by Ras. We have identified downstream targets for Ras family members and new targets of the kinase cascade activated by Ras. Using biochemical, molecular and cell biological approaches, we are investigating how these targets which we have identified impact the ability of Ras to control cell growth, cell survival and cell differentiation.
We also study the Akt1 and Akt2 proteins. The Akt or Protein Kinase B serine/threonine kinases are commonly amplified and activated in a variety of human tumors. Activation of Akt kinases is emerging as a major mechanism by which human tumors become resistant to apoptosis. A focus of my lab is to decipher the signaling pathways regulated by the Akt kinases. We have identified novel partners for Akt and, using a variety of experimental approaches, we are working to further our understanding of the importance of each of these substrates in cell survival and cell transformation.
2001-2005 American Chemical Society Research Scholar
Vojtek, A. B., Haarer, B., Field, J., Gerst, J., Pollard, T. D., Brown, S., and Wigler, M. (1991). Evidence for a functional link between profilin and CAP in S. cerevisiae. Cell 66, 497-505.
Vojtek, A. B., Hollenberg, S., and Cooper, J. (1993). Mammalian Ras interacts directly with the serine/threonine kinase Raf. Cell 74, 205-214.
Fabian, J. R., Vojtek, A. B., Cooper, J. A., and Morrison, D. K. (1994). A single amino acid change in Raf-1 inhibits Ras binding and alters Raf-1 function. Proc. Natl. Acad. Sci. 91, 5982-5986.
Vojtek, A. B. and Cooper, J. A. (1995). Rho family members: Activators of MAP kinase cascades. Cell 82, 527-529.
Graham, S. M., Vojtek, A. B., Huff, S. Y., Cox, A. D., Clark, G. J., Cooper, J. A., and Der, C. J. (1996). TC21 is activated by Ras guanine nucleotide exchange factors but causes transformation by Raf-independent signaling pathways. Mol. Cell Biol. 16, 6132-6140.
Chantry, D., Vojtek, A. B., Kashishian, A., Holtzman, D., Wood, C., Gray, P., Cooper, J. and Hoekstra, M. (1997). p110delta: a novel phosphatidylinositol 3-kinase subunit which associates with p85 and which is expressed predominantly in leukocytes. J. Biol. Chem. 272, 19236-19241.
Winkler, D., Johnson, J., Cooper, J. and Vojtek, A. B. (1997). Identification and characterization of mutations in H-Ras that selectively decrease binding to cRaf. J. Biol. Chem. 272, 24402-9.
Vojtek, A. B. and Der, C. J. (1998). Increasing complexity of the Ras signaling pathway. J. Biol. Chem. 273, 19925-19928.
Guan, K-L., Figueroa, C., Brtva, T., Taylor, J., Barber, T., Zhu, T. and Vojtek, A.B. (2000). Negative Regulation of the B-Raf serine/threonine kinase by Akt. J. Biol. Chem. 275, 27354-59.
Figueroa, C., Taylor, J. and Vojtek, A.B. (2001) PRA1 is a receptor for prenylated small GTPases. J. Biol. Chem. 276, 28219-28225.
Murphy, G. A., Graham, S. M., Morita, S., Reks, S. E., Rogers-Graham, K.,Vojtek, A. B., Kelley, G., and Der, C. J. (2002). Involvement of phosphatidylinositol 3-kinase, but not RalGDS, in TC21/R-Ras2-mediated transformation. J. Biol. Chem. 277, 9966-9975.
Yu, J-Y., Taylor, J., DeRuiter, S., Vojtek, A. B., and Turner, D.L. (2003). Simultaneous inhibition of GSK3α and GSK3β with hairpin siRNA expression vectors. Molecular Therapy 7, 228-236.
Vojtek, A. B., Taylor, J., DeRuiter, S., Yu, J.-Y. and Turner, D.L. (2003). Akt regulates basic helix-loop-helix/coactivator complex formation and activity during neurogenesis.Molecular and Cellular Biology 23, 4417-27.
Figueroa, C. and Vojtek, A. B. (2003). Akt negatively regulates translation of the ternary complex factor Elk-1. Oncogene 22, 5554-5561.
Figueroa, C., Tarras, S., Taylor, J. and Vojtek, A. B. Akt2 negatively regulates assembly of the POSH-MLK-JNK signaling complex. J. Biol. Chem., in press.
Vojtek, A. B., Taylor, J., DeRuiter, S., Yu, J.-Y. and Turner, D. L. (2003) Akt regulates basic helix-loop-helix/coactivator complex formation and activity during neurogenesis. Molecular and Cellular Biology 23, 4417. PMID: 12808085
Figueroa, C., Tarras, S., Taylor, J. and Vojtek, A. B. (2003) Akt2 negatively regulates assembly of the POSH-MLK-JNK signaling complex. J. Biol. Chem. 278, 47922. PMID: 14504284
Chung, K-H., Hart, C. C., Al-Bassam, S., Avery, A., Taylor, J., Patel, P. D., Vojtek, A. B., and Turner, D. L. (2006) Polycistronic RNA polymerase II expression vectors for RNA interference based on BIC/miR-155. Nucleic Acids Research Apr 13; 3 (7): e53 PMID: 16614444
Avery, A. Figueroa, C. and Vojtek, A. B. (2007) UNC-51-like kinase regulation of fibroblast growth factor receptor substrate 2/3. Cellular Signaling 19, 177. PMID: 16887332
Taylor, J., Chung, K-H., Figueroa, C., Zurawski, J., Dickson, H. M., Brace, EJ., Avery, A. W., Turner, D. L., and Vojtek, A. B. (2008) The scaffold protein POSH regulates axon outgrowth. Mol. Biol. Cell 19, 5181-5192. PMCID: 2592661