title: The formation and activity of PP2A holoenzymes do not depend on the isoform of the catalytic subunit.
abstract: The protein phosphatase 2A holoenzyme is composed of one catalytic C subunit, one regulatory/scaffolding A subunit, and one regulatory B subunit. The core enzyme consists of A and C subunits only. The A and C subunits both exist as two closely related isoforms, alpha and beta. The B subunits belong to four weakly related or unrelated families, designated B, B', B", and B"', with multiple members in each family. The existence of two A and two C subunit isoforms permits the formation of four core enzymes, AalphaCalpha, AalphaCbeta, AbetaCalpha, and AbetaCbeta, and each core enzyme could in theory give rise to multiple holoenzymes. Differences between Calpha and Cbeta in expression and subcellular localization during early embryonic development have been reported, which imply that Calpha and Cbeta have different functions. To address the question of whether these differences might be caused by enzymatic differences between Calpha and Cbeta, we purified six holoenzymes composed of AalphaCalpha or AalphaCbeta core enzyme and B subunits from the B, B', or B" families. In addition, we purified four holoenzymes composed of AbetaCalpha or AbetaCbeta and B'alpha1 or B"/PR72. The phosphatase activity of each purified form was assayed using myelin basic protein and histone H1 as substrates. We found that Calpha and Cbeta have identical phosphatase activities when associated with the same A and B subunits. Furthermore, no difference was found between Calpha and Cbeta in binding A or B subunits. These data suggest that the distinct functions of Calpha and Cbeta are not based on differences in enzymatic activity or subunit interaction. The implications for the relationship between the structure and function of Calpha and Cbeta are discussed.
authors.affiliation: Department of Pathology, University of California at San Diego, La Jolla 92093, USA.
authors.forename: Jin
authors.initials: J
authors.lastname: Zhou
authors.forename: Huong T
authors.initials: HT
authors.lastname: Pham
authors.forename: Gernot
authors.initials: G
authors.lastname: Walter
mesh_terms: D000595:Amino Acid Sequence; D020134:Catalytic Domain; D002460:Cell Line; D006801:Humans; D010749:Phosphoprotein Phosphatases / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D011233:Precipitin Tests; D054648:Protein Phosphatase 2
chemical_list: D010749:Phosphoprotein Phosphatases; D054648:Protein Phosphatase 2