A <i>Drosophila</i>‐centric view of protein tyrosine phosphatases

Hatzihristidis, Teri; Desai, Nikita; Hutchins, Andrew P.; Meng, Tzu‐Ching; Tremblay, Michel L.; Miranda‐Saavedra, Diego

doi:10.1016/j.febslet.2015.03.005

Cited by 24 publications

(21 citation statements)

References 253 publications

(296 reference statements)

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“…Protein that contains the PTP signature motif (CX 5 R) was then used as the query in BLASTP search against NCBI sequence repository to identify their paralogs. B. mori PTPs were classified into subfamilies according to their orthologous PTPs in human and fruit fly (Alonso et al, 2004;Hatzihristidis et al, 2015).…”

Section: Ptp Identification and Classificationmentioning

confidence: 99%

Characterization of a protein tyrosine phosphatase as a host factor promoting baculovirus replication in silkworm, Bombyx mori

Wang

Xue

et al. 2016

Developmental & Comparative Immunology

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The relevance of protein tyrosine phosphatase (PTP) to host-pathogen interaction is highlighted in mammalian studies, whereas less is known in insects. Here we presented the categorization of the PTP complement of silkworm and characterized their homologous relationship with human and fruit fly PTPs. Among the 36 PTP genes, ptp-h, which was proposed to be the origin of baculovirus ptp belongs to atypical VH1-like dual-specific PTP subset and encodes a catalytic active protein. The maximum expression level of Bmptp-h was at 5th instar and in fat body. Bombyx mori nucleopolyhedrovirus (BmNPV) infection potently induced its expression in silkworm larvae and in BmE cells. Knock-down of Bmptp-h by RNA interference significantly inhibited viral replication, and over-expression enhanced viral replication as determined by viral DNA abundance and BmNPV-GFP positive cells. These results suggest that BmPTP-h might be one of the host factors that is beneficial to baculovirus infection by promoting viral replication.

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Section: Ptp Identification and Classificationmentioning

confidence: 99%

Characterization of a protein tyrosine phosphatase as a host factor promoting baculovirus replication in silkworm, Bombyx mori

Wang

Xue

et al. 2016

Developmental & Comparative Immunology

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“…They are closely associated with the regulation of various intracellular signaling and cellular processes by controlling protein-protein interaction, protein stability, and enzyme activity (Ardito et al, 2017;Hunter, 1995). The Drosophila genome contains 44 PTPs, which are less than half of 109 PTPs encoded by the human genome (Hatzihristidis et al, 2015). The 44 Drosophila PTP proteins can be divided into four subgroups: 37 class I PTPs that include 16 classical PTPs and 21 dual-specificity phosphatases (DUSPs), four class II low molecular weight-protein tyrosine phosphatases (LMW-PTPs), two class III CDC25 proteins, and one eyes-absent phosphatase (Hatzihristidis et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

Structural and Biochemical Characterization of the Two Drosophila Low Molecular Weight-Protein Tyrosine Phosphatases DARP and Primo-1

Lee

Shin

et al. 2020

Molecules and Cells

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The Drosophila genome contains four low molecular weightprotein tyrosine phosphatase (LMW-PTP) members: Primo-1, Primo-2, CG14297, and CG31469. The lack of intensive biochemical analysis has limited our understanding of these proteins. Primo-1 and CG31469 were previously classified as pseudophosphatases, but CG31469 was also suggested to be a putative protein arginine phosphatase. Herein, we present the crystal structures of CG31469 and Primo-1, which are the first Drosophila LMW-PTP structures. Structural analysis showed that the two proteins adopt the typical LMW-PTP fold and have a canonically arranged P-loop. Intriguingly, while Primo-1 is presumed to be a canonical LMW-PTP, CG31469 is unique as it contains a threonine residue at the fifth position of the P-loop motif instead of highly conserved isoleucine and a characteristically narrow active site pocket, which should facilitate the accommodation of phosphoarginine. Subsequent biochemical analysis revealed that Primo-1 and CG31469 are enzymatically active on phosphotyrosine and phosphoarginine, respectively, refuting their classification as pseudophosphatases. Collectively, we provide structural and biochemical data on two Drosophila proteins: Primo-1, the canonical LMW-PTP protein, and CG31469, the first investigated eukaryotic protein arginine phosphatase. We named CG31469 as DARP, which stands for Drosophila ARginine Phosphatase.

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“…Eya is thus the prototype of a novel class of eukaryotic protein phosphatases. Several recent reviews compare the distinguishing features of aspartyl-based versus thiolbased "classic" eukaryotic protein tyrosine phosphatases (43)(44)(45)(46).The discovery that Eya proteins have intrinsic protein tyrosine phosphatase activity raised many questions about how dephosphorylation of specific substrates might contribute to Eya's transcriptional functions and/or reveal completely new roles for Eya in other cellular processes. Below I consider the extent to which these questions have been answered and the new challenges that have emerged.…”

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confidence: 99%

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Multiple Functions of the Eya Phosphotyrosine Phosphatase

Rebay

2016

Molecular and Cellular Biology

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Eyes absent (Eya), a protein conserved from plants to humans and best characterized as a transcriptional coactivator, is also the prototype for a novel class of eukaryotic aspartyl protein tyrosine phosphatases. This minireview discusses recent breakthroughs in elucidating the substrates and cellular events regulated by Eya's tyrosine phosphatase function and highlights some of the complexities, new questions, and surprises that have emerged from efforts to understand how Eya's unusual multifunctionality influences developmental regulation and signaling. Drosophila Eyes absent (Eya), the founding member of the Eya family, was molecularly defined in 1993 as a novel nuclear protein with essential roles in retinal cell survival and differentiation (1). Four years later, three key findings heightened interest in Eya family proteins. First, three mammalian Eya homologues, Eya1 Eya2, and Eya3, were identified and found to be expressed in the lens and nasal placodes, raising the possibility that the developmental program of eye specification is conserved between invertebrates and mammals (2, 3); the fourth vertebrate Eya gene, Eya4, was identified 2 years later (4). Functional conservation of Eya proteins was further emphasized by the demonstration that expression of murine Eya2 partially restores eye development in Drosophila eya mutants (5). Second, the discovery that loss-offunction mutations in Eya1 produced the ear, kidney and craniofacial defects associated with the autosomal-dominant disease branchio-oto-renal (BOR) syndrome (6-8) highlighted Eya's critical and pleiotropic roles in human development and disease. Third, parallel studies in Drosophila and in mammalian cultured cells revealed a molecular function for Eya as a transcriptional coactivator (5, 9-12). Eya is recruited to transcriptional complexes via a direct interaction between its highly conserved ϳ270-amino-acid (aa) C-terminal motif, the Eya domain (ED) (Fig. 1), and Six family homeodomain DNA binding proteins. Together, Eya and Six operate as a composite transcription factor, with Six providing DNA binding specificity and the N-terminal half of Eya conferring transactivation.In addition to the many similarities, mammalian and Drosophila Eya proteins show a striking difference in subcellular localization. In contrast to Drosophila Eya, which appears constitutively nuclear (13), mammalian Eya proteins show significant cytoplasmic accumulation and rely on binding to Six for nuclear recruitment and retention (11,(13)(14)(15)(16)(17)(18)(19)(20). Although initially dismissed as reflecting two slightly different mechanisms for regulating Eyamediated transcriptional events, in retrospect, as discussed later in this minireview, this observation seems to have foretold a much more profound functional divergence between mammalian and fly Eya proteins.Subsequent molecular genetic studies positioned Eya and Six as central players within a conserved network of transcription factors that is referred to as the retinal determination (RD) network (reviewed in refer...

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A Drosophila‐centric view of protein tyrosine phosphatases

Cited by 24 publications

References 253 publications

Characterization of a protein tyrosine phosphatase as a host factor promoting baculovirus replication in silkworm, Bombyx mori

Characterization of a protein tyrosine phosphatase as a host factor promoting baculovirus replication in silkworm, Bombyx mori

Structural and Biochemical Characterization of the Two Drosophila Low Molecular Weight-Protein Tyrosine Phosphatases DARP and Primo-1

Multiple Functions of the Eya Phosphotyrosine Phosphatase

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