Biography
Susan Taylor is a professor in the Department of Chemistry and Biochemistry and the Department of Pharmacology at UCSD. She is also an HHMI investigator. She studies the structure and function of protein kinases focusing in particular on cAMP-dependent protein kinase and has been a major contributor to our understanding of signal transduction. She received her Ph.D. at Johns Hopkins University and then carried out her postdoctoral studies at the MRC Laboratory in Cambridge, England. She joined the UCSD campus in the mid 1970s and has spent her entire academic career at UCSD. Her crystal structure of the PKA catalytic subunit in 1991 has served as a prototype for the entire protein kinase superfamily. Her subsequent structure of the regulatory subunits and most recently of holoenzyme complexes serve as a paradigm for second messenger signaling. In addition to her scientific achievements, Taylor has had a lifelong commitment to training young scientists. She is a strong advocate for interdisciplinary training and has worked to promote this both locally and nationally. She is a past president of ASBMB and has been involved nationally in advocacy for science and science education at many levels.
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PKA: Prototype for the Evolution of Regulation
Abstract:
cAMP is and ancient stress signal that has been conserved from man, In most eukaryotic cells, the major receptor for cAMP is the regulatory (R) subunit of cAMP-dependent protein kinase (PKA). In the absence of cAMP the R subunit shields the catalytic © subunit and renders it inactive. cAMP binding to the R-subunit unleashes the catalytic activity of the C-subunit. The structure of the C-subunit has served as a prototype for the entire protein kinase superfamily, defining the family not only as a catalyst but also as a scaffold protein that communicates with many other proteins. As one of the largest superfamilies that is linked to many diseases, it is also a prototype for understanding the origins of disease and for developing new therapeutic strategies. The regulatory subunits, on the other hand, define the cAMP binding domain which, like cAMP itself, is also ancient. By solving structures of complexes between R and C, we define for the first time the enormous dynamic range of this signaling module and reveal how it functions not only as the receptor for cAMP but also as a regulator of biological function. Thus in PKA two major signaling mechanisms converge - signaling by protein phosphorylation and signaling through the second messenger, cAMP. To understand the origins of these two mechanisms and to appreciate how widespread they are, we have delved into the world of microbial metagenomics. We find that the catalytic machinery of the eukaryotic protein kinases is widespread and highly conserved throughout the microbial world whereas its unique and sophisticated regulation is a highly evolved feature of the eukaryotic proteins. This conserved mechanism of phosphorylation, used for small molecules and proteins, is thus a prominent regulatory mechanism in the microbial world. cAMP and its binding domain is also a highly conserved signaling mechanism where we find that this highly dynamic molecule is regulating hundreds of functions. It is linked not only to many DNA binding domains but also to many other proteins including many enzymes and transporters. By delving into the origins of PKA, we have uncovered widespread conservation of the mechanisms that allow any cell to respond to environmental stress.
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