Krebs, Edwin

As early as 1938, it was known that glycogen phosphorylase existed in two forms the less active phosphorylase b and the more active phosphorylase a. In 1956, Edwin Krebs and Edmond Eischer reported that a converting enzyme could convert phosphorylase b to phosphorylase a. Three years later, Krebs and Eischer demonstrated that the conversion of phosphorylase b to phosphorylase a involved covalent phosphorylation, as in Eigure 15.17. 

This protein kinase (known as protein kinase A or PK-A) has an R2C2 quaternary structure that binds 3, 5 -cAMP at its dimeric regulatory (R) subunit with resultant release of two catalytic (C) subunits. The free energy of hydrolysis of the cychc nucleotide activator is large (AG 13 kcal/mol) and allows the 3, 5 -cAMP to be virtually irreversibly converted to AMP by the action of a specific phosphodiesterase. This protein kinase, originally discovered by the Nobelists Edwin Krebs and Edward Fischer, is now considered to be the prototype for over two thousand members of the protein kinase superfamily. 

Any of a broad class of phosphoryl-transfer enzymes [EC 2.7.1.x] that catalyze the ATP-dependent phosphorylation of proteins, most often occurring at seryl, threo-nyl, and tyrosyl residues. These enzymes are central participants in cellular signal transduction pathways, and their discovery and recognition as primary control components of the cell culminated in the award of the 1992 Nobel Prize in Medicine and Physiology to American enzymologists Edwin Krebs and Edward Fischer. There is reason to believe that approximately 2% of the coding sequences in the human genome specify some 2000 different kinases that phosphorylate protein substrates. The prototypical enzyme is known as 3, 5 -cAMP-stimulated protein kinase (or, protein kinase A). See specific protein kinase... 

Glycogen phosphorylase was the first enzyme shown to be regulated via protein phosphorylation (Krebs, 1959). In recognition of their trad-blazing work, Edwin Krebs and Edmond Fisher were rewarded the Nobel prize for Chemistry in 1992. 

Edmond H. Fischer and Edwin G. Krebs Physiology/Medicine Reversible protein phosphorylation in biological regulation... 

The Coris found that the interconversion of phosphor-ylases a and b is catalyzed by another enzyme, and subsequent work by Earl Sutherland showed that this process is under hormonal control. In muscle, conversion of phosphorylase b to a is stimulated by epinephrine in liver, it is stimulated by both epinephrine and the pancreatic hormone glucagon. The structural basis for the difference between the two forms of phosphorylase remained unknown until the late 1950s, when Edwin Krebs and Edmund Fischer showed that phosphorylase a has a phosphate on serine 14. This phosphate is absent in the b form of the enzyme. Krebs and Fischer also showed that the kinase that catalyzes the addition of the phosphate is itself regulated by a phosphorylation catalyzed by another enzyme, the cAMP-dependent protein kinase ... 

Reversible chemical modification of enzymes, which was discovered in 1955 by Edmond Fischer and Edwin Krebs [58], is a more prevalent mechanism for cellular signaling switching. Fischer and Krebs showed that enzymes can be turned from an inactive form to an active form via phosphorylation of certain residues of the protein. Enzymes that catalyze phosphorylation (addition of a phosphate group coupled with ATP or GTP hydrolysis) are called protein kinases. Enzymes that catalyze dephosphorylation (which is not the reverse reaction of the phosphorylation) are called phosphatases. For example, a protein tyrosine phosphatase is an enzyme that catalyzes the removal of a phosphate group from a tyrosine residue in a phosphorylated protein [57],... 

Cyclic AMP (= cAMP) (cyclic nucleotide) Earl Sutherland (USA, Nobel Prize, Medicine, 1971, cAMP as second messenger) Edwin Krebs Edmond Fischer (USA, Nobel Prize, Medicine, 1992, PKA)... 

Edwin Krebs Edmond Fischer (USA, Nobel Prize, Medicine,... 

Donal A. Walsh and Edwin G. Krebs Author Index—Subject Index... 

Vols. 17- edited byPaul D. Boyer and Edwin G. Krebs. 

D. E. Koshland, Jr. 1, 10, 18 John S. Kovach 5 Gisela Kramer 20 Edwin G. Krebs 5, 16, 18 H. A. Krebs 1, 18 Nurith Kurn 9 D. A. Kyriakidis 15 M. R. Lakshmanan 18 M. Daniel Lane 8, 18 Henry A. Lardy 18 Joseph Lamer 3 Michel Lazdunski 6 P. J. Lea 20 Robert J. Lefkowitz 17 Albert L. Lehninger 18 Luis F. Leloir 18 James F. Lenney 17 Alexander Levitzki 10 Heng-Chun Li 21 Anthony W. Linnane 2 Fritz Lipmann 18 John M. Lowenstein 18 W. C. Lucchesi 15 Ronald W. McCune 15... 

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