Activity modulation of the fast and slow isozymes of human cytosolic low-molecular-weight acid phosphatase (ACP1) by purines

Dissing, J.; Rangaard, Bjarne; Christensen, Ulla

doi:10.1016/0167-4838(93)90291-x

Cited by 30 publications

(25 citation statements)

References 55 publications

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“…Furthermore, it has been demonstrated (Stefani et al, 1993) that the 5-16 phosphotyrosines present in the N-terminal peptide of human B3P are more efficiently dephosphorylated by f isoforms than by s isoforms [K m (mM) 1.4→0.4; V max (µmol·min -1 ·mg -1 ) 68→10.5]. In light of that mentioned above, our data show that f isoforms, which are more sensitive to oxidative damage compared to s isoforms (Luffman and Harris, 1967;Fisher and Harris, 1971;Bottini et al, 1971b), are likely to undergo inhibition by Vfe more than that reported in the last column of Table 1, where the f activity is calculated reducing it by the same proportion of s as reported by Dissing et al (1993) and where the much higher inhibition of f isoforms compared to s isoforms is not taken into consideration. Therefore, considering that the values of f isoform activities in the presence of Vfe will be certainly lower than those that we have calculated here (i.e., AA = 6.42; CA = 3.64; CC = 5.00), the real f activity associated with ACP 1 AA, ACP 1 CA, ACP 1 CC genotypes will reach extremely low values.…”

Section: Discussionsupporting

confidence: 60%

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Association between ACP1 genetic polymorphism and favism

Polzonetti¹,

Passini²,

Lucarini³

2011

Genet. Mol. Res.

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Section: Discussionsupporting

confidence: 60%

“…We also reported the f isoforms' mean activity of ACP 1 phenotypes calculated according to Dissing et al (1993 Values assuming that the activity of both f and s isoforms is reduced by the same percentage.…”

Section: Resultsmentioning

confidence: 99%

Association between ACP1 genetic polymorphism and favism

Polzonetti¹,

Passini²,

Lucarini³

2011

Genet. Mol. Res.

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“…Activation studies of the wild-type isoenzymes and the HPTP-B mutants by cGMP were performed using the procedure outlined by Dissing et al (19). The activity at saturation, V m Ј, is presented as an increased percentage in activity relative to what is seen without cGMP.…”

Section: Resultsmentioning

confidence: 99%

“…Both isoenzyme forms have been isolated from rat, chicken, Xenopus laevis, and Drosophila (8 -13), whereas the single Tritrichomonas fetus enzyme is similar to HPTP-A (14) and the Mycobacterium tuberculosis, yeast, and bovine enzymes are similar to HPTP-B (15)(16)(17)(18). The human isoenzymes exhibit a dramatically different response to a variety of purine molecules (19,20). In particular, adenine has been shown to inhibit HPTP-A and activate HPTP-B, whereas hypoxanthine activates HPTP-A with little to no effect on HPTP-B.…”

mentioning

confidence: 99%

Crystal Structure of the Human B-form Low Molecular Weight Phosphotyrosyl Phosphatase at 1.6-Å Resolution

Zabell

Schroff

Bain

et al. 2006

Journal of Biological Chemistry

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The crystal structure of HPTP-B, a human isoenzyme of the low molecular weight phosphotyrosyl phosphatase (LMW PTPase) is reported here at a resolution of 1.6 Å . This high resolution structure of the second human LMW PTPase isoenzyme provides the opportunity to examine the structural basis of different substrate and inhibitor/activator responses. The crystal packing of HPTP-B positions a normally surface-exposed arginine in a position equivalent to the tyrosyl substrate. A comparison of all deposited crystallographic coordinates of these PTPases reveals three atomic positions within the active site cavity occupied by hydrogen bond donor or acceptor atoms on bound molecules, suggesting useful design elements for synthetic inhibitors. A selection of inhibitor and activator molecules as well as small molecule and peptide substrates were tested against each human isoenzyme. These results along with the crystal packing seen in HPTP-B suggest relevant sequence elements in the currently unknown target sequence.Tyrosine phosphorylation and dephosphorylation are critical components of eukaryotic signaling. The superfamily of protein-tyrosine phosphatases (PTPases) 2 is defined in part by a canonical CX 5 R(S/T) active site motif (P-loop), and can be divided into families based on substrate specificity and protein size (1-3). Following the classification scheme of Alonso et al. (1), the receptor-like PTPases such as CD45 (4) and non-receptor PTPases such as PTP1B (5) are subdivisions of the class I Cys-based family, multidomain proteins where the canonical phosphatase domain is roughly 30 kDa. The low molecular weight (LMW) PTPase, a soluble 18-kDa protein with essentially no sequence similarity to the other families beyond the active site P-loop (6), is the only member of the class II Cys-based family. Two isoenzyme forms of the LMW PTPase are expressed in humans, HPTP-A and HPTP-B, identical in sequence except for an mRNA splice variant sequence corresponding to residues 40 -73 (7).Although all PTPases are thought to have the same basic mechanism, the families show marked differences in substrate specificity and small molecule modulation. Within the class II family those differences can be sorted into either an HPTP-A or HPTP-B type response. Both isoenzyme forms have been isolated from rat, chicken, Xenopus laevis, and Drosophila (8 -13), whereas the single Tritrichomonas fetus enzyme is similar to HPTP-A (14) and the Mycobacterium tuberculosis, yeast, and bovine enzymes are similar to HPTP-B (15-18). The human isoenzymes exhibit a dramatically different response to a variety of purine molecules (19,20). In particular, adenine has been shown to inhibit HPTP-A and activate HPTP-B, whereas hypoxanthine activates HPTP-A with little to no effect on HPTP-B. It has also been reported that the rat isoenzyme ACP2 is activated 900% by cGMP, whereas the activity of isoenzyme ACP1 is unchanged (21). Adenine has been co-crystallized with the Saccharomyces cerevisiae LMW PTPase, and the structure suggests a basis for . The adeni...

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“…The physiological role of the yeast enzymes is still unknown but the mammalian LMW-PTP shows a broad range of substrates including the PDGF and insulin receptors [11], caveolin [12], and the p190Rho GAP [13]. The activation of mammalian LMW-PTP by purines or purine derivatives, nucleosides, and nucleotides has been described [14][15][16], together with the activity modulation of human LMW-PTP by adenine and hypoxanthine [17]. The mechanism of the activation of the LMW-PTP by purines is not completely understood.…”

mentioning

confidence: 99%

The in vivo tyrosine phosphorylation level of yeast immunophilin Fpr3 is influenced by the LMW-PTP Ltp1

Magherini

Gamberi

Paoli

et al. 2004

Biochemical and Biophysical Research Communications

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Tyr-phosphorylation in Saccharomyces cerevisiae is essential in controlling the activity of MAP kinase regulating mating, pseudohyphal growth, and cell wall biosynthesis. Yeast serves as a model system for studying the biological function of many protein kinases and PTPs. Two LMW-PTP from yeast have been cloned, namely, Ltp1 from S. cerevisiae and Stp1 from Schizosaccharomyces pombe. The sequences of both enzymes are relatively similar to those of the mammalian LMW-PTP. Recently we showed that the yeast immunophilin Fpr3 interacts with Stp1 and its dephosphorylated state induces a growth defective phenotype. Here we show the phosphatase activity of Ltp1 on Fpr3 and we demonstrated that Tyr 184 is the residue phosphorylated on in vivo Fpr3. We also described the marked activation of Ltp1 by adenine in S. cerevisiae proteome and determined in vivo the influence of tyrosine phosphorylation on Fpr3 localization. Ó 2004 Elsevier Inc. All rights reserved.Keywords: LMW-PTP; Saccharomyces cerevisiae Ltp1; Immunophilin Fpr3; Tyrosine phosphorylation in yeast Phosphotyrosyl protein phosphatases are structurally diverse enzymes that have fundamental roles in cellular processes, including effects on metabolism, cell proliferation, and differentiation [1]. Although in budding yeast conventional tyrosine kinases are not present, Zhu et al.[2] using a chip technology identified 27 kinases able to phosphorylate poly-Glu-Tyr, a typical artificial substrate of bona fide tyrosine kinases. Moreover, Tyrphosphorylation has been shown in Saccharomyces cerevisiae to be essential in controlling the activity of MAP (mitogen-activated-protein) kinases which, in turns regulate mating, osmosensing pseudohyphal and invasive growth, spore wall assembly, and cell wall biosynthesis [3]. The low-molecular weight protein tyrosine phosphatases (LMW-PTP) are single-domain cytosolic enzymes with molecular masses of approximately 18 kDa. The active site sequence motif of these enzymes has a conserved (V/I)CXGNXCRS sequence. Members of this family have been identified in a wide variety of organisms, including bacteria, yeast, rat, bovine, and human [4][5][6][7][8], suggesting that these enzymes have important cellular functions. Yeast serves as a simple, but often useful, model system for studying the biological function of many protein kinases and PTPs. Two LMW-PTP from yeast have been cloned, namely, Ltp1 from S. cerevisiae [9] and Stp1 from Schizosaccharomyces pombe [10]. The sequences of both enzymes are relatively similar to those of the mammalian LMW-PTP, with identity of 42% and 39% for the Stp1 and Ltp1, respectively. The physiological role of the yeast enzymes is still unknown but the mammalian LMW-PTP shows a broad range of

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Activity modulation of the fast and slow isozymes of human cytosolic low-molecular-weight acid phosphatase (ACP1) by purines

Cited by 30 publications

References 55 publications

Association between ACP1 genetic polymorphism and favism

Association between ACP1 genetic polymorphism and favism

Crystal Structure of the Human B-form Low Molecular Weight Phosphotyrosyl Phosphatase at 1.6-Å Resolution

The in vivo tyrosine phosphorylation level of yeast immunophilin Fpr3 is influenced by the LMW-PTP Ltp1

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