Cleavage of the signaling mucin Msb2 by the aspartyl protease Yps1 is required for MAPK activation in yeast.
Signaling mucins are cell adhesion molecules that activate RAS/RHO guanosine triphosphatases and their effector mitogen-activated protein kinase (MAPK) pathways. We found that the Saccharomyces cerevisiae mucin Msb2p, which functions at the head of the Cdc42p-dependent MAPK pathway that controls filamentous growth, is processed into secreted and cell-associated forms. Cleavage of the extracellular inhibitory domain of Msb2p by the aspartyl protease Yps1p generated the active form of the protein by a mechanism incorporating cellular nutritional status. Activated Msb2p functioned through the tetraspan protein Sho1p to induce MAPK activation as well as cell polarization, which involved the Cdc42p guanine nucleotide exchange factor Cdc24p. We postulate that cleavage-dependent activation is a general feature of signaling mucins, which brings to light a novel regulatory aspect of this class of signaling adhesion molecule.
Vadaie
Nadia
N
Department of Biological Sciences, State University of New York at Buffalo, Buffalo, NY 14260, USA.
Dionne
Heather
H
Akajagbor
Darowan S
DS
Nickerson
Seth R
SR
Krysan
Damian J
DJ
Cullen
Paul J
PJ
D016282:Aspartic Acid Endopeptidases / Q000096:biosynthesis / Q000378:metabolism*; D004789:Enzyme Activation; D004790:Enzyme Induction; D020690:GTPase-Activating Proteins / Q000737:chemistry / Q000378:metabolism*; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins; D020935:MAP Kinase Signaling System; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009077:Mucins / Q000378:metabolism*; D010455:Peptides / Q000378:metabolism; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D017434:Protein Structure, Tertiary; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000201:enzymology*; D029701:Saccharomyces cerevisiae Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism*; D015398:Signal Transduction
D020690:GTPase-Activating Proteins; D020662:Guanine Nucleotide Exchange Factors; D047908:Intracellular Signaling Peptides and Proteins; C076360:MSB2 protein, S cerevisiae; D009077:Mucins; D010455:Peptides; D029701:Saccharomyces cerevisiae Proteins; D020928:Mitogen-Activated Protein Kinases; D016282:Aspartic Acid Endopeptidases; C499266:YPS1 protein, S cerevisiae