Naghibalhossaini Fakhraddin, Stanners Clifford P
Department of Biochemistry and McGill Cancer Centre, McGill University, Montreal, Quebec, Canada H3G 1Y6.
J Cell Sci. 2004 Feb 15;117(Pt 5):761-9. doi: 10.1242/jcs.00903. Epub 2004 Jan 20.
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.
癌胚抗原（CEA）家族中的糖基磷脂酰肌醇（GPI）锚定相对于跨膜（TM）锚定导致了截然不同的功能获得，包括抑制分化和失巢凋亡、破坏组织结构以及促进肿瘤发生。由CEA的羧基末端外显子所决定的CEA GPI锚定，在赋予这些功能变化的能力方面表现出生物学特异性。CEA家族的GPI锚定在灵长类动物辐射过程中似乎独立进化了两次，其方式表明是从更原始的TM锚定的癌胚抗原相关细胞黏附分子1（CEACAM1）进化而来。我们在此表明，当今人类CEACAM1的TM外显子中只需极少的突变就能实现高效的GPI锚定以及CEA GPI锚定的生物学特异性，即赋予GPI锚定的CEA的分化阻断功能。因此，这种锚定的改变可能是在进化过程中产生免疫球蛋白超家族成员分子功能的根本变化的一种相对简便的方式。
