Evolution of the Metazoan Protein Phosphatase 2C Superfamily

Abstract

Members of the protein phosphatase 2C (PP2C) superfamily are Mg(2+)/Mn(2+)-dependent serine/threonine phosphatases, which are essential for regulation of cell cycle and stress signaling pathways in cells. In this study, a comprehensive genomic analysis of all available metazoan PP2C sequences was conducted. The phylogeny of PP2C was reconstructed, revealing the existence of 15 vertebrate families which arose following a series of gene duplication events. Relative dating of these duplications showed that they occurred in two active periods: before the divergence of bilaterians and before vertebrate diversification. PP2C families which duplicated during the first period take part in different signaling pathways, whereas PP2C families which diverged in the second period display tissue expression differences yet participate in similar signaling pathways. These differences were found to involve variation of expression in tissues which show higher complexity in vertebrates, such as skeletal muscle and the nervous system. Further analysis was performed with the aim of identifying the functional domains of PP2C. The conservation pattern across the entire PP2C superfamily revealed an extensive domain of more than 50 amino acids which is highly conserved throughout all PP2C members. Several insertion or deletion events were found which may have led to the specialization of each PP2C family.

Virulence Factors Encoded by Legionella longbeachae Identified on the Basis of the Genome Sequence Analysis of Clinical Isolate D-4968

“…The L. pneumophila genome encodes a large number and wide variety of eukaryote-like proteins (1, 26, 40). The acquisition of eukaryote-like genes can be (50,86). In eukaryotes, PP2Cs are involved in several cell regulation and cell signaling processes, including p53 activation (86), implying that L. longbeachae may use the serine/threonine phosphatase activity of the LLB_2177 protein to modulate similar processes in its host cells.…”

“…The acquisition of eukaryote-like genes can be (50,86). In eukaryotes, PP2Cs are involved in several cell regulation and cell signaling processes, including p53 activation (86), implying that L. longbeachae may use the serine/threonine phosphatase activity of the LLB_2177 protein to modulate similar processes in its host cells. Three L. longbeachae genes, LLB_2053, LLB_3045, and LLB_3686 (Table 5 and data not shown), encode proteins containing the Ras family motif (Pfam00071), a small GTP-binding domain rarely found in bacteria.…”

Substrate-dependent metal preference of PPM1H, a cancer-associated protein phosphatase 2C: comparison with other family members

“…in the majority of enzymes, exchange between two metals may lead to some differences in biochemical interactions, thereby altering the properties of enzymes (Maguire and Cowan 2002). With these facts in mind, the deficiency in the detailed characterization of the PP2C enzymatic activity except for PP2Ca and the emerging significant roles of mammalian PP2Cs (Stern et al 2007) further evoked our interest in the characters of the PP2C family.…”

Small molecule activators of pre-mRNA 3′ cleavage

“…As a class, they are expected to have similar structures and active sites (Stern et al 2007) and would therefore be expected to share sensitivity to the same inhibitors. While several of these paralogs are known to localize to the nucleus (Moorhead et al 2007), one in particular, PP2Cg (PPM1G), has been found to play a role in pre-mRNA splicing (Murray et al 1999;Allemand et al 2007), which is in turn coordinated with 39 cleavage (Niwa et al 1990;Kyburz et al 2006;Millevoi et al 2006).…”