Cell signaling through membrane mucins.
MUC1 and MUC4 are the two membrane mucins that have been best characterized. Although they have superficially similar structures and have both been shown to provide steric protection of epithelial surfaces, recent studies have also implicated them in cellular signaling. They act by substantially different mechanisms, MUC4 as a receptor ligand and MUC1 as a docking protein for signaling molecules. MUC4 is a novel intramembrane ligand for the receptor tyrosine kinase ErbB2/HER2/Neu, triggering a specific phosphorylation of the ErbB2 in the absence of other ErbB ligands and potentiating phosphorylation and signaling through the ErbB2/ErbB3 heterodimeric receptor complex formed in the presence of neuregulin. In contrast, MUC1 has a highly conserved cytoplasmic tail, which binds beta-catenin, a key component of adherens junctions and a regulator of transcription, in a process that is tightly regulated by MUC1 phosphorylation. The specific localization of these membrane mucins to the apical surfaces of epithelial cells suggests that their signaling functions may be important as sensor mechanisms in response to invasion or damage of epithelia.
Carraway
Kermit L
KL
Department of Cell Biology and Anatomy, University of Miami School of Medicine, Miami, FL 33101, USA. kcarrawa@med.miami.edu
Ramsauer
Victoria P
VP
Haq
Bushra
B
Carothers Carraway
Coralie A
CA
D000595:Amino Acid Sequence; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism*; D006801:Humans; D008024:Ligands; D008954:Models, Biological; D008969:Molecular Sequence Data; D018396:Mucin-1 / Q000378:metabolism; D055264:Mucin-4; D009077:Mucins / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D015398:Signal Transduction
D008024:Ligands; D018396:Mucin-1; D055264:Mucin-4; D009077:Mucins; D018719:Erb-b2 Receptor Tyrosine Kinases; C524658:MUC4 protein, human