Signaling mucins: The new kids on the MARK block

Signaling mucins are an emerging group of cell adhesion receptors that activate mitogen-activated protein kinase (MARK) pathways at the level of RAS/RHO. Recent discoveries on several fronts, including in the model eukaryote budding yeast, have broadened our understanding of this family of signaling molecules. Progress in characterizing three signaling mucins, MUC1, Muc4, and Msb2, points to a surprising degree of functional overlap in the regulation and mechanism-of-activation of these molecules. The prevailing new insight is one of receptor activation by proteolytic cleavage that closely mirrors the developmental signaling factor, Notch. The unexpected parallels between signaling mucins and Notch spark new questions about mucin activation and provoke a double take at this fledgling class of signaling adhesion molecule.