Research Summary

Posttranslational modifications play a central role in regulating cellular functions. A diverse range of proteomics methods have enabled on a global scale the detection, characterization and quantitation of many types of modification (e.g. phosphorylation). Despite their fundamentally important role in cellular function, characterization of prenylated proteins such as RAS from cells and tissues has not been achieved. RAS proteins play a central role in the uncontrolled growth associated with cancer. It is estimated that more than 30% of all cancers are driven by RAS mutations. The RAS proteins are posttranslationally modified by farnesene, an isoprenyl group that targets it to the plasma membrane where it acts as a GTPase switch to regulate cell proliferation. Membrane association is essential for RAS activity. In addition to farnesene's role, the amino acid sequence at the C-terminus plays an important role in membrane association. KRAS 4B contains a C-terminal sequence consisting of a polybasic region that is known to stabilize its membrane association. Accordingly, membrane association of KRAS has become a potential target for drug development but there are currently no good ways to isolate and study this in detail on the molecular level.

I have developed a selective chemical targeting method that will allow us to isolate RAS and other prenyl-modified proteins proteins along with their C-terminal peptides from cells so that we can characterize their amino acid sequence and posttranslational modifications in normal and diseased states. This method will enable study of the associations of these peptides/proteins with membranes and other proteins.


University of Texas, Austin, BA, 05/1974, Biology
University of Tennessee, Knoxville, PhD, 06/1979, Biochemistry
The Johns Hopkins University, Baltimore, Postdoctoral, 06/1984, Biophysics

Selected Publications

  1. Wilkins JA, Kaasik K, Chalkley RJ, Burlingame AL. Characterization of Prenylated C-terminal Peptides Using a Thiopropyl-based Capture Technique and LC-MS/MS. Mol Cell Proteomics. 2020;19(6):1005-1016.
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  2. Li Y, Chen Y, Xiang R, Ciuparu D, Pfefferle LD, Horváth C, Wilkins JA. Incorporation of single-wall carbon nanotubes into an organic polymer monolithic stationary phase for mu-HPLC and capillary electrochromatography, Anal Chem., 77(5), 1398-1406 (2005).
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  3. Li Y, Xiang R, Horváth C, Wilkins JA. Capillary electrochromatography of peptides on a neutral porous monolith with annular electroosmotic flow generation, Electrophoresis, 25(4-5), 545-553 (2004).
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