Choel Kim, Ph.D.
Department of Pharmacology
Department of Biochemistry & Molecular Biology
SCBMB Executive Committee Member
Baylor College of Medicine
Education and Awards:
B.S., 1995, Biology, University of California, San Diego
M.S., 1996, Biology, University of California, San Diego
Ph.D., 2002, Chemistry, University of California, San Diego
Postdoctoral Fellow, 2002-2008, Howard Hughes Medical Institute at Susan Taylor Laboratory, University of California, San Diego
- Signal transduction
- Protein-Protein Recognition
- Assembly of Higher Order Signal Transduction Complexes
- Localized Cyclic Nucleotide Signaling
To survive, a cell must be able to sense its ever-changing environment and adapt with an appropriate response or a set of responses. In particular, cellular events that require rapid and amplified responses, such as neurotransmitter release, hormone secretion and muscle contraction, need highly organized and dynamic sets of proteins with coordinated interactions. While we are accumulating biochemical and structural information on individual signaling components, understanding these molecules in the context of larger signaling assembly remains an important challenge that has yet to be realized.
Cyclic nucleotide (cAMP and cGMP) dependent protein kinases are broad-specificity kinases that can phosphorylate a large range of substrates and require mechanisms to achieve their specificity. In this theme, we have come to appreciate that these proteins and their substrates are not randomly scattered throughout the cell. Instead they are localized and exist as part of larger signaling complexes that are assembled near the sites of phosphorylation such as ion channels and co-transporters or near organelles such as the mitochondria and golgi. Often this targeting is mediated by a family of scaffolding proteins, called Kinase Anchoring Proteins, which can bind not only kinases, but other signaling components such as phosphatases, phospodiesterases and other proteins.
Using cyclic nucleotide (cAMP and cGMP) dependent protein kinases as model systems, Dr. Choel is interested in understanding these signaling proteins not only as single proteins, but also as integral components of larger signaling assemblies. His lab will pursue the answers to the following questions:
- What are the molecular determinants for binding cyclic nucleotides that lead to activation?
- What are the anchoring proteins specific for NO/cGMP signaling pathway?
- How do different anchoring proteins differentiate pathway-specific kinases?
- How are different signaling components functionally organized and linked to other pathways?
They will answer these questions using interdisciplinary techniques such Biophysical and biochemical methods, Molecular biology, X-ray crystallography and NMR, Single molecule cryoEM and Small angle x-ray scattering.
- Kim JJ, Casteel DE, Huang G, Kwon TH, Ren RK, Zwart P, Headd JJ, Brown NG, Chow DC, Palzkill T and Kim C. Co-crystal structures of PKG Iß (92-227) with cGMP and cAMP reveal the molecular details of cyclic-nucleotide binding. PLoS One, 6(4):e18413 (2011). PubMed
- Taylor SS, Kim C, Cheng CY, Simon H, Brown JW and Kannan N. Signaling through cAMP and CAMP-dependent protein kinase: Diverse strategies for Drug Design. Biochemis Biophys Acta, 1784(1):16-26 (2007). PubMed
- Taylor SS, Eggers CT and Kim C. Multivalent Integration of Local and Global Signaling through PKA, Calcineurin, AKAP79/150, and L-Type Calcium Channels. Cell Science Reviews, 4:16-24 (2007).
- Kim C, Cheng CY, Saldanha AS and Taylor SS. PKA-lα Holoenzyme Structure: Dynamic conformational change of RIα Reveals Mechanism for cAMP-dependent Activation. Cell, 130:1032-43 (2007) PubMed
- Kinderman FS, Kim C, van Daake S, Pham BQ, Spraggon G, Jennings PA and Taylor SS. A Dynamic Mechanism for AKAP Binding to RII Isoforms of cAMP-Dependent Protein Kinase. Molecular Cell, 24:397-408 (2006). PubMed
- Gullingsrud J, Kim C, Taylor SS and McCammon JA. Dynamic Binding of PKA Regulatory subunit (RI α). Structure, 14:141-149 (2006). PubMed
- Taylor SS, Kim C, Vigil D, Haste NM, Yan J, Wu J and Anand GS. Dynamics of Signaling by PKA. Biochem Biophys Acta, 1754(1-2):25-37 (2006). PubMed
For more publications, see listing on PubMed.
Address: Baylor College of Medicine
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