Cadherin-dependent Adhesion
Classical cadherins are important proteins for cells to bind in the body (‘’in vivo’’) where they commonly stabilize cell–cell junctions known as adherens junctions. Cadherins stabilize adherens junctions through the interaction of the cadherin cytoplasmic domains with catenin proteins, such as p120-catenin, beta-catenin and alpha-catenin. Catenins, in turn, bind to the actin cytoskeleton. Binding of these proteins to the actin cytoskeleton prevents actin from growing (a process known as polymerization) and therefore keeps cells stationary. Cadherins regulate cell–cell adhesion during development of the body and in adult tissue. Disruption of cadherin proteins, by genetic alteration or by changes to the structure or function of the protein, has been linked to tumor progression. Notably, PTPmu regulates the adhesion of cells to the classical cadherins. PTPmu likely regulates cadherin-dependent adhesion by interacting with both cadherins and catenins via PTPmu’s cytoplasmic domain. To support this assertion, PTPmu has been shown to interact with and/or dephosphorylate many signaling proteins involved in regulating the cadherin-catenin complex, including p120 catenin, and E-cadherin (CDH1 (gene)) and N-cadherin (CDH2). PTPmu has also been shown to interact with the c-Met hepatocyte growth factor receptor, a protein that is also localized to adherens junctions. Although p120 catenin is a potential substrate of PTPmu, others have suggested that the interaction between PTPmu and catenins is only indirect through E-cadherin. α3β1 integrin and the tetraspanin CD151 regulate PTPmu gene expression to promote E-cadherin-mediated cell–cell adhesion.
In addition to catenins and cadherins, PTPmu dephosphorylates PIPKIγ90 and nectin-3 (PVRL3) to stabilize E-cadherin-based adherens junctions. PTPmu also dephosphorylates another cell junction protein, connexin 43. The interaction between connexin 43 and PTPmu increases gap junction communication.
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