Protein phosphatase 4 – from obscurity to vital functions

AbstractProtein phosphatase 4 (Ppp4) is a ubiquitous serine/threonine phosphatase in the PPP family that is now recognised to regulate a variety of cellular functions independently of protein phosphatase 2A (PP2A). Regulatory subunits (R1 and R2) have been identified in mammals that interact with the catalytic subunit of Ppp4 (Ppp4c) and control its activity. Ppp4c–R2 complexes play roles in organelle assembly; not only are they essential for maturation of the centrosome, but they are also involved in spliceosomal assembly via interaction with the survival of motor neurons (SMNs) complex. Several cellular signalling routes, including NF-κB and the target of rapamycin (TOR) pathways appear to be regulated by Ppp4. Emerging evidence indicates that Ppp4 may play a role in the DNA damage response and that Ppp4c–R1 complexes decrease the activity of a histone deacetylase, implicating Ppp4 in the regulation of chromatin activities. Antitumour agents, cantharidin and fostriecin, potently inhibit the activity of Ppp4. Orthologues of mammalian Ppp4 subunits in Saccharomyces cerevisiae confer resistance to the anticancer, DNA-binding drugs, cisplatin and oxaliplatin

Polymerase chain reactions using Saccharomyces, Drosophila and human DNA predict a large family of protein serine/threonine phosphatases

AbstractUsing the polymerase chain reaction (PCR) to examine the protein serine/threonine phosphatase (PP) family which includes PP1, PP2A and PP2B, we have identified two, seven, and four novel protein phosphate genes in Saccharomyces cerevisiae, Drosophila melanogaster and Homo sapiens, respectively. Consequently, the genes in the PP1/PP2A/PP2B family now number 11, 15 and 12 in these species respectively, and the data predicts still more unidentified phosphatases in higher eukaryotes. The PCR analyses also point to the presence in Drosophila and mammals of three or more different genes encoding PP2B, the enzyme recently identified as the target of certain immunosuppressant drugs

Isolation and sequence analysis of a cDNA clone encoding the entire catalytic subunit of phosphorylase kinase

AbstractSynthetic oligonucleotides have been used to isolate a 1.85 kb clone containing the full length coding sequence for the catalytic subunit of rabbit skeletal muscle phosphorylase kinase from a cDNA library constructed in λgt10. Sequence analysis of the clone predicted an amino acid sequence in agreement with a published primary structure. Inspection of the codon usage revealed a strong preference for G or C nucleotides at the third codon position as found for several other skeletal muscle proteins. This cDNA clone should facilitate identification of functional domains, including the calmodulin-binding site, and investigation of the molecular basis of X-linked phosphorylase kinase deficiencies

Molecular cloning and chromosomal localization of a novel Drosophila protein phosphatase

AbstractA 1.0 kilobase cDNA coding for the complete amino acid sequence of a putative protein phosphatase (314 amino acid residues, molecular mass 36 kDa) has been isolated from a Drosophila head cDNA library. The cDNA hybridises to a single site on the right arm of the second chromosome at cytological position 55A1–3. The deduced sequence of the protein, designated protein phosphatase-Y, is homologous to the catalytic subunits of Drosophila and rabbit protein phosphatase- 1α (64 and 59% identity, respectively) and rabbit protein phosphatase-2A (39% identity). These and other comparisons demonstrate that this novel enzyme is not the Drosophila counterpart of mammalian protein phosphatases 1, 2A, 2B, 2C or X

PPP1R6, a novel member:Of the family of glycogen-targetting subunits of protein phosphatase 1

AbstractA complementary DNA encoding a novel human protein phosphatase 1 (PP1) glycogen-targetting subunit of molecular mass 33 kDa has been sequenced. PPP1R6 is 31% identical to the glycogen-targetting subunit (GL) of PP1 from rat liver, 28% identical to the N-terminal region of the glycogen-targetting subunit (GM) from human skeletal muscle and 27% identical to glycogen-targetting subunit PPP1R5. Unlike human PPP1R5 and its murine homologue PTG, whose mRNAs are most abundant in skeletal muscle, heart and liver, PPP1R6 is present at similar levels in a wide variety of tissues. The PPP1R6 is associated with glycogen in muscle but is not subject to the same modes of covalent and allosteric regulation as GM and GL