Focus on phosphorylation

Credit: Generated using Polyview-3D / A. Porollo, J. Meller (2007) Versatile Annotation and Publication Quality Visualization of Protein Complexes Using POLYVIEW-3D" /> Credit: Generated using Polyview-3D / A. Porollo, J. Meller (2007) Versatile Annotation and Publication Quality Visualization of Protein Complexes Using POLYVIEW-3D The paper: J. Villén et al., "Large-scale p

Jan 1, 2009
Elie Dolgin
<figcaption> Credit: Generated using Polyview-3D / A. Porollo, J. Meller (2007) Versatile Annotation and Publication Quality Visualization of Protein Complexes Using POLYVIEW-3D</figcaption>
Credit: Generated using Polyview-3D / A. Porollo, J. Meller (2007) Versatile Annotation and Publication Quality Visualization of Protein Complexes Using POLYVIEW-3D

The paper:

J. Villén et al., "Large-scale phosphorylation analysis of mouse liver," Proc Natl Acad Sci, 104:1488-93, 2007. (Cited in 75 papers)

The finding:

Steven Gygi and colleagues at the Harvard Medical School combined an array of analytical methods—including phosphopeptide enrichment, high performance mass spectrometry, and an optimized data-sorting algorithm—to generate the first systematic survey of post-translational protein phosphorylations in a single organ, the mouse liver.

The impact:

Gygi's team discovered more than 5,000 phosphorylation sites across some 2,300 proteins in the liver that had not been previously identified. "It's an order of magnitude higher [than found in earlier studies], so you really have a good overview of what's happening," says Heribert Hirt at the Plant Genomics Research Unit (URGV) in Evry, France.

The surprise:

In general, phosphorylation is much more frequent at the C-terminal region than anywhere else on the protein. Since integral membrane proteins are usually oriented with the C-terminus in the intracellular space, these regions are likely targeted by kinases, says Harvard's Judit Villén, the study's lead author. As such, enhanced phosphorylation could help set off signaling cascades within the cell.

The datasets:

In 2008, Gygi's team used similar techniques to identify cell cycle-regulated protein phosphorylation in human cells, and analyzed phosphorylation in fruit fly embryos and fission yeast. Villén has complete unpublished phosphoproteome maps for eight additional mouse tissues, including brain, pancreas, lung, and testis.

Number of liver phosphorylation sites identified:
2004: 26 (Rapid Commun Mass Spectrosc, 18:2169-76, 2004)
2006: 339 (J Proteome Res, 5:98-104, 2006)
2007: 5,635 (Proc Natl Acad Sci, 104:1488-93, 2007)