Defining Cells One Pathway At a Time
August 11, 2008
One of the most daunting challenges facing biology is to define the signal transduction pathways that twist, turn, and bifurcate through our cells like highway grids to connect the molecular traffic on the outer surface to the two-way flow of information in the nuclear membrane. If the last century of research is any guide, most of the major fundamental discoveries in signal transduction will occur first in the more experimentally tractable model organisms, such as roundworm, and fruit fly. As published online on June 30 in The Journal of Cell Biology, NIDCR grantees and colleagues may have brought to light another fundamental discovery in brewer's yeast, a distant eukaryotic cousin to humans. Msb2 is a cell-adhesion molecule called a signaling mucin that functions at the head of the MAPK pathway, a major regulatory route that triggers various outcomes in brewer's yeast including filamentous growth. The scientists discovered that Msb2 is cleaved and then processed into secreted and cell-associated forms, marking a novel MAPK activation mechanism. As the researchers explained, "This discovery, coupled with the fact the secreted domain of Msb2p is inhibitory, suggests a mechanism where processing and release of the extracellular domain activates the protein . . . We speculate that cleavage-dependent activation may be a general feature of mucin receptors."