Fields of Research
Intracellular signaling
Molecular basis of disease
Protein structure and function
Research Summary
I am researching the binding of different AKAPs to the two distinct classes of protein kinase A.
One arm of my project involves phylogenic analysis of the evolution of AKAPs. Looking at sequences of extant orthologs, I have been able to trace the evolution of different AKAPs, as well as the points where various protein interaction domains first originated
The second arm of my project involves analyzing the AKAP helices which bind PKA, and performing targeted mutations to alter their selectivity. I use Amber molecular dynamics simulations to model these interactions (and virtually screen mutants) to assess specific anchor points, and their necessity for binding.
I then create the mutations, both in full length constructs for functional analysis in cells (such as FRAP microscopy to measure PKA anchoring, measuring hormone levels in the presence of mutated AKAPs, and co-IPs) and GST fusion helices for in vitro binding assays.
Research Statement
A-kinase anchoring proteins (AKAPs) regulate signaling events by constraining kinases, phosphatases, and their substrates at specific locations in the cell. I am interested in interrogating molecular motifs which facilitate protein-protein interactions, and studying the evolutionary development and specialization of these proteins.
Awards and Honors
Faculty
- Building:
- Health Sciences Center K Wing
- Room:
- K326
- Box:
- 357280
- Phone:
- 206-221-0517
- Web Link:
- https://depts.washington.edu/phcol/faculty/scott.php
Lab
- Building:
- Health Sciences Center K Wing
- Room:
- K326
- Box:
- 357280
- Phone:
- 206-221-0517
- Web Link:
- https://depts.washington.edu/phcol/faculty/scott.php
Select Publications
Gopalan J, Omar MH, Roy A, Cruz NM, Falcone J, Jones KN, Forbush KA, Himmelfarb J, Freedman BS, Scott JD. Targeting an anchored phosphatase-deacetylase unit restores renal ciliary homeostasis. Elife. 2021 Jul 12;10:e67828. doi: 10.7554/eLife.67828. PMID: 34250905; PMCID: PMC8291974.
Bogdan D*, Falcone J*, Kanjiya MP, Park SH, Carbonetti G, Studholme K, Gomez M, Lu Y, Elmes MW, Smietalo N, Yan S, Ojima I, Puopolo M, Kaczocha M. Fatty acid-binding protein 5 controls microsomal prostaglandin E synthase 1 (mPGES-1) induction during inflammation. J Biol Chem. 2018 Apr 6;293(14):5295-5306. doi: 10.1074/jbc.RA118.001593. Epub 2018 Feb 13. PubMed PMID: 29440395; PubMed Central PMCID: PMC5892576.
Yan S, Elmes MW, Tong S, Hu K, Awwa M, Teng GYH, Jing Y, Freitag M, Gan Q, Clement T, Wei L, Sweeney JM, Joseph OM, Che J, Carbonetti GS, Wang L, Bogdan DM, Falcone J, Smietalo N, Zhou Y, Ralph B, Hsu HC, Li H, Rizzo RC, Deutsch DG, Kaczocha M, Ojima I. SAR studies on truxillic acid mono esters as a new class of antinociceptive agents targeting fatty acid binding proteins. Eur J Med Chem. 2018 Jun 25;154:233-252. doi: 10.1016/j.ejmech.2018.04.050. Epub 2018 May 26. PubMed PMID: 29803996; PubMed Central PMCID: PMC5999033.
Publications
