Edwin Krebs dies
Nobel Laureate uncovered the mechanism of reversible protein phosphorylation
Edwin G. Krebs, winner of the linkurl:1992 Nobel Prize for Physiology or Medicine;http://nobelprize.org/nobel_prizes/medicine/laureates/1992/krebs-autobio.html for first describing the process of reversible protein phosphorylation, died at 91 on December 21 of complications from heart failure.
A longtime professor at the University of Washington, Krebs shared the Nobel with his colleague Edmond Fischer. Krebs' research served as "major foundation stones for what is now the 'signaling field,'" linkurl:Bruce Kemp,;http://www.svi.edu.au/index.cfm?objectID=CA4FAAFE-0173-FE61-3D63E73FDA3BC811 a former postdoc of Krebs and professor at St. Vincent's Institute of Medical Research in Australia, wrote in an email to The Scientist
Image: University of Washington
Krebs (not to be confused with the 1953 Nobel Laureate Hans Adolf Krebs, not related) was born in Lansing, Iowa in 1918 and spent much of his childhood in Illinois. He attended the University of Illinois for undergraduate studies and Washington University for medical school. There Krebs studied with linkurl:Carl and Gerty Cori,;http://nobelprize.org/nobel_prizes/medicine/laureates/1947/index.html who won the Nobel Prize in 1947 for discovering phosphorylase, the enzyme that catalyzes the production of glucose-1-phosphate from glycogen.
In 1948, Krebs joined the biochemistry department at the University of Washington in Seattle. Aside from an eight-year stint at the University of California, Davis, Krebs remained at Washington his entire career, the latter half as a member of the department of pharmacology.
After his arrival in Washington, Krebs paired up with his UW colleague Edmond Fischer to study phosphorylation reactions in rabbit skeletal muscle. They found that phosphorylase kinase and phosphatase were responsible for adding or removing, respectively, a phosphate from phosphorylase and controlling the enzyme's activity. "Because phosphorylase was calcium-dependent this provided a link between muscle contraction and metabolism," Kemp wrote.
After illustrating reversible phosphorylation, Krebs' lab went on to discover cyclic AMP-dependent protein kinase.
Krebs moved to UC Davis to chair the department of biological chemistry in 1968 and stayed until 1977. During this time, Krebs's lab discovered that protein kinases determined their particular substrates based on surrounding amino acid residues, particularly arginine residues.
Twelve years after he left UC Davis and returned to the University of Washington, Krebs won the 1989 linkurl:Lasker Award;http://www.laskerfoundation.org/awards/library/1989basic.shtml for Basic Medical Research. Three years later he and Fischer won the 1992 linkurl:Nobel Prize;http://nobelprize.org/nobel_prizes/medicine/laureates/1992/presentation-speech.html in Physiology or Medicine for contributions to "the opening up of novel insight into basic protein regulations at all levels and in all cells."
"That was the most amazing experience because of the outpouring of enthusiasm for his winning the award," linkurl:Lee Graves,;http://www.med.unc.edu/~lmg/ who was a postdoc with Krebs during that time, told The Scientist
. Krebs and Fischer "really were the fathers of this field."
Graves, who is now a professor at the University of North Carolina, said he considers Krebs an academic grandfather, because his father, Donald Graves, was a graduate student with Krebs during the 1950s. "I really was fortunate to have had that opportunity to spend [time] with him," Graves said. "To hear some of the stories of when they first worked on phosphorylation--there was a lot of skepticism, and how much an effort it was."
Arthur Edelman, a former postdoc of Krebs who is now a linkurl:professor;http://deptdirectory.med.buffalo.edu/profile/facultyprofile.asp?ht=dd&fid=0F70L4CIN at the State University of New York, Buffalo, said Krebs continued to do important work after his prizes. "Clearly he was well advanced in his career, while other investigators might be slowing down at this point." But in the 1990s, Krebs turned his attention to the mitogen-activated protein kinase (MAPK) signaling cascade, including characterizing parts of the cascade and exploring the pathway's relationship to other kinase pathways. "It struck me how great this work was," Edelman said.
For nearly three decades he held editorial positions for the Journal of Biological Chemistry
. He is survived by his wife Deedy and three children.
Krebs was known as a hands-off advisor who was judicious with giving out compliments. "He was not given to effusive statements," Edelman said. Still, he was "immensely likeable" and admired by his lab members, Kemp wrote. "The only time Ed ever came into the laboratory on a Saturday, we were so pleased to be noticed for our diligence," Kemp wrote, "but it came with an unexpected cost. He was there to centrifuge some terrible homemade wine and we had to taste it in little glass beakers."
Krebs was also a cautious and thoughtful scientist who did not get carried away by the excitement of discovery, Edelman said. "What happens in science is we all get enamored of our own work...and Ed would ask, 'how important is this really?' He wasn't selling his own work, but thoughtfully evaluating it."
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[18th January 2007]*linkurl:Pioneering protein chemist dies;http://www.the-scientist.com/blog/display/56131/
[3rd November 2009]*linkurl:Focus on phosphorylation;http://www.the-scientist.com/article/display/55305/