Structure of PP2A

PP2A exists in cells as two major forms: holoenzyme and core enzyme [8,9]. The core enzyme consists of a 36-kDa catalytic C subunit and a 65-kDa regulatory A subunit. Holoenzymes are composed of a core enzyme to which one of several regulatory B subunits is bound (Fig. 1). It has been proposed that the core enzyme is an artifact of enzyme isolation and does not exist in cells. This is highly unlikely, however, as under the gentlest conditions of enzyme purification the core enzyme represents one-third to one-half of total cellular PP2A [8,9]. Recently, it has been suggested that the core enzyme is unstable unless associated with a regulatory B subunit [10]. It remains to be seen, however, whether in these experiments the absence of core enzyme is a consequence of eliminating all B subunits, which is not physiological, or whether it has resulted from toxic experimental conditions. The A and C subunits exist as two iso-forms: Aa and Ap and Ca and CP, respectively. Thus, four core enzymes, AaCa, ApCa, AaCp, and ApCp, might exist in cells that could have distinct substrate specificities and distinct abilities to interact with regulatory subunits or other cellular proteins. Therefore, the question of whether core enzymes are a physiological reality is an important one.

The B subunits fall into four families, designated B, B' (also called B56), B", and B''' which appear unrelated by sequence alignment. The B family has four members: Ba, Bp, By, and B§. The B' family consists of five genes encoding B'a, B'p, B'y, B'5, and B'e. Including isoforms and splice variants, there are a total of at least eight B' subunits. The B" family has four members, designated PR48, PR59, PR72, and PR130. The latter two are splice variants of the same gene. The B''' family has two members: striatin and SG2NA. The existence of so many regulatory subunits suggests that PP2A is a highly regulated phosphatase and that its various forms fulfill

Figure 1 Model of PP2A.

numerous distinct functions. Another class of proteins able to associate with PP2A core enzyme are tumor (T) antigens encoded by polyoma viruses. Their binding domains on the A subunit overlap with those of B subunits. T antigens play a key role in neoplastic transformation by polyoma viruses, and their association with PP2A is essential for transformation [11].

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