The Big Picture of Synaptic Phosphorylation

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Science  04 Mar 2005:
Vol. 307, Issue 5714, pp. 1379
DOI: 10.1126/science.307.5714.1379b

Collins et al. have used advances in mass spectrometry and strategies to enrich phosphopeptides in cell extracts to carry out a proteomic analysis of phosphorylation events in synaptosomes (synaptic terminals) from the mouse brain. Although phosphorylation events are known to be important in synaptic signaling and have been studied extensively, these results suggest that traditional studies have barely scratched the surface. Of the almost 300 phosphorylation sites identified, 92% had not been described previously. Many proteins exhibited multiple phosphorylation sites (as many as 30), so the 300 sites were distributed among only 79 proteins, half of which were not known to be phosphorylated before.

The authors used peptide arrays along with literature mining and bioinformatic analysis to assign kinases likely to target these sites. Most substrates appear to be targets of multiple kinases; one group of kinases appears to phosphorylate their target proteins at multiple sites, and another appears to hit just one site per substrate. A relatively small number of kinases appears to account for much of the phosphorylation observed. In fact, nine kinases appear to be responsible for more than 250 of the phosphorylation sites. — LBR

J. Biol. Chem. 280, 5972 (2005).

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