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Rabbit anti-AF-6 (N-term); Polyclonal antibody specific to Mouse. This antibody is validated in Western Blot, and Immunohistochemistry. AF-6, also known as afadin, is expressed in a variety of cell types. At least 5 isoforms of this protein are produced by alternative splicing and the 'canonical' sequence is designated as l-afadin. Chromosomal aberration of the MLLT4 gene (encoding AF-6) is associated with acute leukemias. AF-6 exists as a homodimer and interacts with various components of the cellular adhesion system, including actin cytoskeleton. Nectin-afadin complex is involved in the formation of cell-cell junctions, such as adherens junctions (AJ) and tight junctions (TJ). AF-6 connects nectins to the cadherin-catenin system at AJs and to the claudin-ZO protein system at TJs. Afadin knock-out mice show embryonic lethality and embryonic stem cells from these mice show increased apoptosis. Nectin-afadin complex is involved in PDGF-induced cell survival, at least through the PI3K-Akt signaling pathway. Proper accumulation of Par complex and activation of cdc42 and aPKC, as well as laminin and integrin alpha 6 and integrin beta 1 deposition were also inhibited by knockout of afadin. This indicates that afadin organizes the formation of cell-cell junctions in early embryonic development. AF-6 is also a key modulator of Wingless⁄Wnt, Ras-Mitogen Activated Protein Kinase (MAPK) and Notch signaling pathways cross-communication. This happens through physical interaction with Ras, Notch and Dishevelled, a key Wingless effector. AF-6 also controls integrin-mediated cell adhesion. This is done at least partially by regulating Rap1 activation through recruitment of both SPA-1 (a Rap1 GTPase-activating protein) and Rap1GTP. These results demonstrate that AF-6 is an important molecule mediating cell-cell adhesion but is also capable of modulating several key signaling pathways.
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