Choel Kim, Ph.D.
Department of Pharmacology
Department of Biochemistry & Molecular Biology
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
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, I am interested in understanding these signaling proteins not only as single proteins, but also as integral components of larger signaling assemblies. My 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?
We 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.
Dr. Kim’s representative publications:
- Susan S. Taylor, Choel Kim, Cecilia Y. Cheng, Simon H. Brown, Jian Wu, Natarajan Kannan (2007) “Signaling through cAMP and CAMP-dependent protein kinase: Diverse Strategies for Drug Design.” Biochemis Biophys Acta.[PubMed] [DOI]
- Susan S. Taylor, Christopher T. Eggers, Choel Kim (2007) "Multivalent Integration of Local and Global Signaling through PKA, Calcineurin, AKAP79/150, and L-Type Calcium Channels.” Cell Science Reviews, 4:16-24.
- Choel Kim, Cecilia y. Cheng, Adrian S. Saldanha, Susan S. Taylor (2007) “PKA-Iα Holoenzyme Structure: Dynamic conformational change of RIα Reveals Mechanism for cAMP-dependent Activation.” Cell, 130:1032-1043.[PubMed] [DOI]
- Francis S. Kinderman, Choel Kim, Sventja van Daake, Bao Q. Pham, Glen Spraggon, Patricia A. Jennings and Susan S. Taylor (2006) “A Dynamic Mechanism for AKAP Binding to RII Isoforms of cAMP-Dependent Protein Kinase.” Molecular Cell, 24: 397-408. [PubMed] [DOI]
- Justin Gullingsrud, Choel Kim, Susan S. Taylor and j. Andrew McCammon (2006) “Dynamic Binding of PKA Regulatory subunit (RI α).” Structure, 14:141-149. [PubMed] [DOI]
- Susan S. Taylor, Choel Kim, Dominico Vigil, Nina M. Haste, Jie Yan, Jian Wu and Ganesh S. Anand (2006) “Dynamics of Signaling by PKA.” Biochem Biophys Acta., 1754(1-2):25-37. [PubMed] [DOI]
- Choel Kim, Xuong Nguyen-Huu and Susan S. Taylor (2005) “Crystal Structure of a Complex between the Catalytic and Regulatory (RIα) Subunits of PKA.” Science, 307:690-696. [PubMed] [DOI]
- Choel Kim, Xuong Nguyen-Huu, Steve Edwards, Maduhudan, Muh-Ching Yee, Glen Spraggon and Stanle E. Mills (2002) “The Crytal Structure of Anthranilate Phosphoribosyltransferase from the enterobacterium Pectobacterium carotovorum.” FEBS Lett. 523(1-3):239-46. [PubMed] [DOI]
- Glen Spraggon, Choel Kim, Xuong Nguyen-Huu, Muh-Ching Yee, Charles Yanofsky and Stanley E. Mills (2001) “The Structures of Antranilate Synthase of Serratia marcescens Crystallized in the Presence of its Substrates, Chorismate and Glutamine, and a Product, Glutamate and (ii) its end product inhibitor L-tryptophan.” Proc. Natl. Acad. Sci. 98:6021. [PubMed]