Adhesion of cells to one another and to extracellular matrix ECM is important during various physiological and pathological processes, such as embryogenesis, wound healing, immune response, and tumor growth. Cell adhesion provides tissue integrity and interaction and has an influence on regulation of cell proliferation, migra- tion, differentiation, and apoptosis [1-3]. Cell adhesion occurs with involvement of adhesive molecules (cad- herins, selectins, connexins, proteoglycans, immu- noglobulins) and extracellular matrix proteins. The struc- ture of cell adhesion proteins is characterized by the pres- ence of the tripeptide RGD (arginyl-glycyl-aspartic acid), which is involved in interaction with specific receptors on the cell surface—integrins [4, 5]. Most adhesion proteins are mosaic, multimodular, and polyfunctional proteins. Each of their modules can function independently, possi- bly through binding with its own membrane receptor. Functionally important modules of these proteins include modules structurally similar to epidermal growth factor (EGF), containing 30-40 amino acid residues (aa), and responsible for the involvement of the proteins in regula- tion of cell proliferation and differentiation [6]. α-Fetoprotein (AFP) is the major oncofetal protein of all mammals and, possibly, all vertebrates [7-9]. It plays an essential role in embryogenesis and carcinogenesis, being involved in the regulation of cell proliferation, dif- ferentiation, and apoptosis. Similarly to cell adhesion proteins, AFP is a mosaic, multimodular, and polyfunc- tional protein. Despite a rather pronounced similarity between the primary structures of AFP and albumin, which are homologous and 40% identical proteins, and common features of their secondary and tertiary struc- tures, AFP is characterized by some specific features lacking in albumin. Intensive studies during the last decade have revealed in AFP some functionally important sites that are absent in albumin. These findings seem to explain specific functions of AFP [10]. The alignment of primary structures of AFP, albumin, and EGF allowed us to detect in AFP a short motif LDSYQCT (aa 14-20) ISSN 0006-2979, Biochemistry (Moscow), 2007, Vol. 72, No. 9, pp. 920-935. © Pleiades Publishing, Ltd., 2007. Original Russian Text © A. A. Terentiev, N. T. Moldogazieva, 2007, published in Biokhimiya, 2007, Vol. 72, No. 9, pp. 1133-1152. 920 Abbreviations: AFP) α-fetoprotein; aa) amino acid; BM) base- ment membrane; ECM) extracellular matrix; EGF) epidermal growth factor; FAK) focal adhesion kinase; ILK) integrin- linked kinase; IGF) insulin-like growth factor; MAPK) mito- gen-activated protein kinase; PDGF) platelet-derived growth factor; PI-3K) phosphatidylinositol-3-kinase; PKB) protein kinase B; RGD) arginyl-glycyl-aspartic acid; RTK) receptor tyrosine kinase; TGF-α) transforming growth factor-α; TNF- α) tumor necrosis factor-α; VEGF) vascular endothelial growth factor. * To whom correspondence should be addressed. Cell Adhesion Proteins and α-Fetoprotein. Similar Structural Motifs as Prerequisites for Common Functions A. A. Terentiev* and N. T. Moldogazieva Russian State Medical University, Department of Biochemistry, ul. Ostrovityanova 1, 117997 Moscow, Russia; fax: (495) 434-0588; E-mail: aaterent@mtu-net.ru; nmoldogazieva@mail.ru Received April 30, 2007 Revision received May 25, 2007 Abstract—This review summarizes and analyzes data on structural and functional relationships between cell adhesion pro- teins and α-fetoprotein (AFP), which play an important role in embryo- and carcinogenesis and act in synergism with growth factors. These two groups of proteins are mosaic, multimodular, and polyfunctional, and each of their modules can function independently through binding with its specific membrane receptor. Most cell adhesion proteins contain modules similar to epidermal growth factor (EGF) and also their repeats, which determine the involvement of these proteins in reg- ulation of cell proliferation, differentiation, and apoptosis. These EGF-like modules are found to include short motifs sim- ilar to the fragment LDSYQCT of human AFP. Both direct and inverted AFP-like motifs are linked through a consensus octapeptide motif CXXGY/FXGX. Such AFP-like motifs of cell adhesion proteins and the tripeptide RGD found in AFP may be structural prerequisites for common functions of these groups of nonhomologous and unrelated proteins. DOI: 10.1134/S0006297907090027 Key words: cell adhesion proteins, α-fetoprotein, structural motifs