TAILIEUCHUNG - Báo cáo khoa học: The role of the SEA (sea urchin sperm protein, enterokinase and agrin) module in cleavage of membrane-tethered mucins

The membrane-tethered mucins are cell surface-associated dimeric or multi-meric molecules with extracellular, transmembrane and cytoplasmic por-tions, that arise from cleavage of the primary polypeptide chain. Following the first cleavage, which may be cotranslational, the subunits remain closely associated through undefined noncovalent interactions. | ềFEBS Journal The role of the SEA sea urchin sperm protein enterokinase and agrin module in cleavage of membrane-tethered mucins Timea Palmai-Pallag1 Naila Khodabukus1 Leo Kinarsky2 Shih-Hsing Leir1 Simon Sherman2 Michael A. Hollingsworth2 and Ann Harris1 1 Paediatric Molecular Genetics Weatheralllnstitute of Molecular Medicine John Radcliffe Hospital Oxford UK 2 Eppley Institute for Research in Cancer and Allied Diseases University of Nebraska MedicalCenter Omaha NE USA Keywords MUC3 MUC12 proteolytic cleavage SEA Correspondence A. Harris Paediatric Molecular Genetics Weatherall Institute of Molecular Medicine John Radcliffe Hospital Oxford OX3 9DS UK E-mail Received 25 January 2005 revised 11 March 2005 accepted 7 April 2005 doi The membrane-tethered mucins are cell surface-associated dimeric or multimeric molecules with extracellular transmembrane and cytoplasmic portions that arise from cleavage of the primary polypeptide chain. Following the first cleavage which may be cotranslational the subunits remain closely associated through undefined noncovalent interactions. These mucins all share a common structural motif the SEA module that is found in many other membrane-associated proteins that are released from the cell surface and has been implicated in both the cleavage events and association of the subunits. Here we examine the SEA modules of three membrane-tethered mucins MUC1 MUC3 and MUC12 which have significant sequence homology within the SEA domain. We previously identified the primary cleavage site within the MUC1 SEA domain as FRPG SVVV a sequence that is highly conserved in MUC3 and MUC12. We now show by site-directed mutagenesis that the F G and S residues are important for the efficiency of the cleavage reaction but not indispensable and that amino acids outside this motif are probably important. These data are consistent with a new model of the MUC1 SEA domain that is based on the .

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