Figure 1. Phosphatases involved in regulation of tight and adherens junctions. 1. The major Ser/Thr phosphatases involved in regulation of junctional proteins are PP1 and PP2A. These are comprised of a catalytic subunit, one or more regulatory ‘B’ subunits, and in the case of PP2A, a structural ‘A’ subunit. Each subunit is present in different isoforms that can impart degrees of variation in enzyme activity, cellular localization, and distribution. 2. The classical protein tyrosine phosphatases (PTPs) involved in regulation of junction proteins are members of the receptor-like or non-transmembrane proteins (gene names in parentheses). The RPTP sub-families i.e., type IIa are listed as R2A, R2B and R3 respectively. The various functional domains of the PTPs represented are identified in the box. While the non-transmembrane PTPs contain a single PTP domain, the receptor-like PTPs contain a catalytically-active, membrane proximal, PTP domain and a membrane-distal PTP domain (PTP pseudo-phosphatase domain) that has residual activity. 3. Tight junction and adherens junction proteins including transmembrane proteins such as the claudins, occludin and cadherins, as well as accessory proteins and cytoskeletal elements that are direct or indirect targets of the described phosphatases, are also represented. For the sake of clarity, specific signaling interactions between the various phosphatases and junctional proteins are not shown.