Protein tyrosine phosphatase RQ is a phosphatidylinositol phosphatase  that can regulate cell survival and proliferation

Oganesian, Anush; Poot, Martin; Daum, Günter; Coats, Scott A.; Wright, Matthew B.; Seifert, Ronald A.; Bowen‐Pope, Daniel F.

doi:10.1073/pnas.1336511100

Cited by 77 publications

(63 citation statements)

References 33 publications

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“…25 PTPRQ is specifically induced within the repopulating glomerular cells, 25 confirming the validity of our approach and was recently identified as a phosphatidylinositol phosphatase. 26 Among all genes of cluster 2, transgelin was most strikingly regulated during anti-Thy1 nephritis. Hardly detectable in normal glomeruli, transgelin mRNA and protein were continuously upregulated up to day 5 after disease induction as shown by microarray and northern-blot analysis or immunostaining, respectively.…”

Section: Discussionmentioning

confidence: 96%

Transgelin is a marker of repopulating mesangial cells after injury and promotes their proliferation and migration

Daniel

Lüdke

Wagner

et al. 2012

Laboratory Investigation

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Mesangial cell (MC) migration is essential during glomerular repair and kidney development. The aim of the study was to identify marker/player for glomerular progenitor/reserve cells migrating into the glomerulus after MC injury and during glomerulogenesis in the rat. Experimental mesangial proliferative nephritis was induced in Sprague Dawley rats by intravenous injection of OX-7 antibody. We investigated mRNA expression profiles in isolated glomeruli from on days 0, 1, 2, 3, and 5 after induction of anti-Thy1 nephritis using Affymetrix microarray technology. Using self-organizing maps, transgelin was identified as a new marker for repopulating glomerular cells. Expression of transgelin during anti-Thy1 nephritis was investigated by northern blot, real-time PCR, western blot, and immunohistochemistry. Migration and proliferation assays using isolated MCs after transgelin knockdown by siRNA were performed to investigate the potential role of transgelin during glomerular repopulation. Transgelin mRNA was not detected in healthy glomeruli. It was strongly upregulated during the repopulation process starting on day 1, continued to be increased until day 5 and disappeared on day 7. Transgelin was specifically expressed at the edge of the migratory front during glomerular repopulation as indicated by transgelin/OX-7 double staining. Transgelin expression was similar in migrating vs non-migrating MCs in vitro. Blocking of transgelin expression by siRNA treatment resulted in inhibition of MC migration and proliferation. Transgelin was also expressed in MCs during glomerulogenesis and in biopsies from patients with IgA nephritis. In conclusion, transgelin in the kidney is upregulated in repopulating MCs in vivo and supports their migratory and proliferative repair response after injury.

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Section: Discussionmentioning

confidence: 96%

Transgelin is a marker of repopulating mesangial cells after injury and promotes their proliferation and migration

Daniel

Lüdke

Wagner

et al. 2012

Laboratory Investigation

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“…Like phogrin, their catalytic domains display relatively low PIPase activities when assayed as soluble catalytic domain fusion proteins despite evidence for biologically significant activity of the full-length protein in vivo. PTPRQ is a transmembrane PIPase that, like phogrin, is a single-pass transmembrane protein in the PTPase family that differs from canonical active PTPases at several sites in the catalytic domain (48). Best characterized of the transmembrane PIPases is a newly recognized group in which a CX 5 R PTPase-like domain is coupled to multiple putative transmembrane domains, similar to those present in voltage-dependent ion channels.…”

Section: The Cytoplasmic Domain Of Phogrin Has Pipase Activity That Imentioning

confidence: 99%

The Neurosecretory Vesicle Protein Phogrin Functions as a Phosphatidylinositol Phosphatase to Regulate Insulin Secretion

Caromile

Oganesian

Coats

et al. 2010

Journal of Biological Chemistry

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Phogrin is a transmembrane protein expressed in cells with stimulus-coupled peptide hormone secretion, including pancreatic beta cells, in which it is localized to the membrane of insulin-containing dense-core vesicles. By sequence, phogrin is a member of the family of receptor-like protein-tyrosine phosphatases, but it contains substitutions in conserved catalytic sequences, and no significant enzymatic activity for phogrin has ever been reported. We report here that phogrin is able to dephosphorylate specific inositol phospholipids, including phosphatidylinositol (PI) 3-phosphate and PI 4,5-diphosphate but not PI 3,4,5-trisphosphate. The phosphatidylinositol phosphatase (PIPase) activity of phogrin was measurable but low when evaluated by the ability of a catalytic domain fusion protein to hydrolyze soluble short-chain phosphatidylinositol phospholipids. Unlike most PIPases, which are cytoplasmic proteins that associate with membranes, mature phogrin is a transmembrane protein. When the transmembrane form of phogrin was overexpressed in mammalian cells, it reduced plasma membrane phosphatidylinositol 4,5-disphosphate levels in a dosedependent manner. When purified and assayed in vitro, the transmembrane form had a specific activity of 142 mol/min/ mol, 75-fold more active than the catalytic domain fusion protein and comparable with the specific activities of the other PIPases. The PIPase activity of phogrin depended on the catalytic site cysteine and correlated with effects on glucose-stimulated insulin secretion. We propose that phogrin functions as a phosphatidylinositol phosphatase that contributes to maintaining subcellular differences in levels of PIP that are important for regulating stimulus-coupled exocytosis of insulin.

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“…PtdIns (3,4,5)P3 has been shown to inhibit apoptosis in various cell types (19,35). PtdIns(3,4,5)P3 activates Akt, an antiapoptotic molecule that can regulate apoptosis by directly controlling members of the apoptotic cascades.…”

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confidence: 99%

Infection with Anaplasma phagocytophilum Activates the Phosphatidylinositol 3-Kinase/Akt and NF-κB Survival Pathways in Neutrophil Granulocytes

et al. 2012

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c Anaplasma phagocytophilum, a Gram-negative, obligate intracellular bacterium infects primarily neutrophil granulocytes. Infection with A. phagocytophilum leads to inhibition of neutrophil apoptosis and consequently contributes to the longevity of the host cells. Previous studies demonstrated that the infection inhibits the executionary apoptotic machinery in neutrophils. However, little attempt has been made to explore which survival signals are modulated by the pathogen. The aim of the present study was to clarify whether the phosphatidylinositol 3-kinase (PI3K)/Akt and NF-B signaling pathways, which are considered as important survival pathways in neutrophils, are involved in A. phagocytophilum-induced apoptosis delay. Our data show that infection of neutrophils with A. phagocytophilum activates the PI3K/Akt pathway and suggest that this pathway, which in turn maintains the expression of the antiapoptotic protein Mcl-1, contributes to the infection-induced apoptosis delay. In addition, the PI3K/Akt pathway is involved in the activation of NF-B in A. phagocytophilum-infected neutrophils. Activation of NF-B leads to the release of interleukin-8 (IL-8) from infected neutrophils, which, in an autocrine manner, delays neutrophil apoptosis. In addition, enhanced expression of the antiapoptotic protein cIAP2 was observed in A. phagocytophilum-infected neutrophils. Taken together, the data indicate that upstream of the apoptotic cascade, signaling via the PI3K/Akt pathway plays a major role for apoptosis delay in A. phagocytophilum-infected neutrophils.

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Protein tyrosine phosphatase RQ is a phosphatidylinositol phosphatase that can regulate cell survival and proliferation

Cited by 77 publications

References 33 publications

Transgelin is a marker of repopulating mesangial cells after injury and promotes their proliferation and migration

Transgelin is a marker of repopulating mesangial cells after injury and promotes their proliferation and migration

The Neurosecretory Vesicle Protein Phogrin Functions as a Phosphatidylinositol Phosphatase to Regulate Insulin Secretion

Infection with Anaplasma phagocytophilum Activates the Phosphatidylinositol 3-Kinase/Akt and NF-κB Survival Pathways in Neutrophil Granulocytes

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