These mice go on to get all the sequelae of aortic stenosis and aortic regurgitation. So the real value of the model is to show progressive heart failure from a stenotic lesion. A Cinderella Protein Neel did not set out to find a model for heart valve disease. Nor was he seeking a new role for Egfr. Although it has become a protein to watch, until recently Shp2 and proteins like it were relegated to the status of cellular housekeepers.
Cells regulate protein activity by adding and removing phosphates.
Kinases put phosphates on while phosphatases, including Shp2, take them off. Until recently, the phosphatases were thought by many to be simply cleaning up after the kinases, which were believed to hold the regulatory reins. That belief had begun to crumble by the early 1990s, thanks in part to the work of another team of HMS researchers. Lizabeth Perkins, currently HMS assistant professor of surgery at Massachusetts General Hospital, but then working in the lab of Norbert Perrimon, Howard Hughes investigator and HMS professor of genetics, demonstrated that the fly homolog of Shp2, the gene corkscrew, actually enhances the signals put out by another protein during embryonic development. Flies lacking the corkscrew protein did not develop proper heads and tails.