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Yale scientists decipher 'wiring pattern' of cell signaling networks

A team of scientists at Yale University has completed the first comprehensive map of the proteins and kinase signaling network that controls how cells of higher organisms operate, according to a report this week in the journal Nature.

The study is a breakthrough in understanding mechanisms of how proteins operate in different cell types under the control of master regulator molecules called protein kinases. Although protein kinases are already important targets of cancer drugs including Gleevec and Herceptin, until recently, it has been difficult to identify the proteins regulated by the kinases.

Led by Michael Snyder, Lewis B Cullman Professor of Molecular, Cellular and Developmental Biology, these researchers focused on the expression and relationship between proteins of the yeast cell "proteome," or the proteins that are active in a cell.

Protein kinases act as regulator switches and modify their target proteins by adding a phosphate group to them. This process, called "phosphorylation," results in altered activity of the phosphorylated protein. It is estimated that 30% of all proteins are regulated by this process.

Using technology developed in Snyder's laboratory, graduate students Jason Ptacek and Geeta Devgan used proteome microarrays to assay the thousands of different proteins in a yeast cell for targets of the protein kinases. The 82 unique kinases, representing the majority of master regulators in the yeast cell, were tested separately with the microarrays to determine which proteins were modified by each kinase.

From the wealth of information generated by these experiments Snyder's team constructed a complex map of the regulatory networks governing the functions and activities of the kinases in the yeast cell. The map sh
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Source:Yale University


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