Minimal mutations are required to effect a radical change in function in CEA family members of the Ig superfamily.
GPI anchorage in the CEA family results in the acquisition of radically different functions relative to TM anchorage, including inhibition of differentiation and anoikis, disruption of tissue architecture and promotion of tumorigenicity. CEA GPI anchors, as determined by the carboxy-terminal exon of CEA, demonstrate biological specificity in their ability to confer these functional changes. CEA family GPI anchorage appears to have evolved twice independently during the primate radiation, in a manner suggestive of evolution from more primitive TM-anchored CEACAM1. We show here that very few mutations in the TM exon of present-day human CEACAM1 are required to give efficient GPI anchorage and the biological specificity of CEA GPI anchors, i.e., to give the differentiation-blocking function of GPI-anchored CEA. Such a change in anchorage could therefore represent a relatively facile means for producing radical change in molecular function of Ig superfamily members during evolution.
Naghibalhossaini
Fakhraddin
F
Department of Biochemistry and McGill Cancer Centre, McGill University, Montreal, Quebec, Canada H3G 1Y6.
Stanners
Clifford P
CP
D000818:Animals; D015703:Antigens, CD / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D000943:Antigens, Differentiation / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D001483:Base Sequence; D002272:Carcinoembryonic Antigen / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules; D002454:Cell Differentiation; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D005434:Flow Cytometry; D017261:Glycosylphosphatidylinositols / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007136:Immunoglobulins / Q000737:chemistry*; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed / Q000235:genetics; D009154:Mutation / Q000235:genetics*; D043265:Phosphatidylinositol Diacylglycerol-Lyase / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D051381:Rats; D017421:Sequence Analysis
D015703:Antigens, CD; D000943:Antigens, Differentiation; C069847:CD66 antigens; D002272:Carcinoembryonic Antigen; D015815:Cell Adhesion Molecules; D017261:Glycosylphosphatidylinositols; D007136:Immunoglobulins; D043265:Phosphatidylinositol Diacylglycerol-Lyase