scholarly journals Tyrosine phosphorylation enhances activity of pneumococcal autolysin LytA

Microbiology ◽  
2014 ◽  
Vol 160 (12) ◽  
pp. 2745-2754 ◽  
Author(s):  
Alistair J. Standish ◽  
Jonathan J. Whittall ◽  
Renato Morona
Keyword(s):  
Tyrosine Phosphorylation ◽  
Protein Tyrosine Phosphatase ◽  
Capsular Polysaccharide ◽  
Regulatory Mechanism ◽  
Tyrosine Phosphatase ◽  
Phosphorylation Site ◽  
Regulatory Proteins ◽  
Amidase Activity ◽  
The Past

Tyrosine phosphorylation has long been recognized as a crucial post-translational regulatory mechanism in eukaryotes. However, only in the past decade has recognition been given to the crucial importance of bacterial tyrosine phosphorylation as an important regulatory feature of pathogenesis. This study describes the effect of tyrosine phosphorylation on the activity of a major virulence factor of the pneumococcus, the autolysin LytA, and a possible connection to the Streptococcus pneumoniae capsule synthesis regulatory proteins (CpsB, CpsC and CpsD). We show that in vitro pneumococcal tyrosine kinase, CpsD, and the protein tyrosine phosphatase, CpsB, act to phosphorylate and dephosphorylate LytA. Furthermore, this modulates LytA function in vitro with phosphorylated LytA binding more strongly to the choline analogue DEAE. A phospho-mimetic (Y264E) mutation of the LytA phosphorylation site displayed similar phenotypes as well as an enhanced dimerization capacity. Similarly, tyrosine phosphorylation increased LytA amidase activity, as evidenced by a turbidometric amidase activity assay. Similarly, when the phospho-mimetic mutation was introduced in the chromosomal lytA of S. pneumoniae, autolysis occurred earlier and at an enhanced rate. This study thus describes, to our knowledge, the first functional regulatory effect of tyrosine phosphorylation on a non-capsule-related protein in the pneumococcus, and suggests a link between the regulation of LytA-dependent autolysis of the cell and the biosynthesis of capsular polysaccharide.

Protein tyrosine phosphatase-α complexes with the IGF-I receptor and undergoes IGF-I-stimulated tyrosine phosphorylation that mediates cell migration

2009 ◽  
Vol 297 (1) ◽  
pp. C133-C139 ◽  
Author(s):  
Shirley C. Chen ◽  
Ranvikram S. Khanna ◽  
Darrell C. Bessette ◽  
Lionel A. Samayawardhena ◽  
Catherine J. Pallen
Keyword(s):  
Cell Migration ◽  
Tyrosine Phosphorylation ◽  
Protein Tyrosine Phosphatase ◽  
Tyrosine Kinases ◽  
Tyrosine Phosphatase ◽  
Phosphorylation Site ◽  
Protein Tyrosine ◽  
Fibroblast Migration ◽  
Igf I ◽  
In Cells

Protein tyrosine phosphatase-α (PTPα) is a widely expressed receptor-type phosphatase that functions in multiple signaling systems. The actions of PTPα can be regulated by its phosphorylation on serine and tyrosine residues, although little is known about the conditions that promote PTPα phosphorylation. In this study, we tested the ability of several extracellular factors to stimulate PTPα tyrosine phosphorylation. The growth factors IGF-I and acidic FGF induced the highest increase in PTPα phosphorylation at tyrosine 789, followed by PMA and lysophosphatidic acid, while EGF had little effect. Further investigation of IGF-I-induced PTPα tyrosine phosphorylation demonstrated that this occurs through a novel Src family kinase-independent mechanism that does not require focal adhesion kinase, phosphatidylinositol 3-kinase, or MEK. We also show that PTPα physically interacts with the IGF-I receptor. In contrast to IGF-I-induced PTPα phosphorylation, this association does not require IGF-I. The interaction of PTPα and the IGF-I receptor is independent of PTPα catalytic activity, and expression of exogenous PTPα does not promote IGF-I receptor tyrosine dephosphorylation, indicating that PTPα does not act as an IGF-I receptor phosphatase. However, PTPα mediates IGF-I signaling, because IGF-I-stimulated fibroblast migration was reduced by ∼50% in cells lacking PTPα or in cells with mutant PTPα lacking the tyrosine 789 phosphorylation site. Our results suggest that PTPα tyrosine phosphorylation can occur in response to diverse stimuli and can be mediated by various tyrosine kinases. In the case of IGF-I, we propose that IGF-I-induced tyrosine 789 phosphorylation of PTPα, possibly catalyzed by the PTPα-associated IGF-I receptor tyrosine kinase, is required for efficient cell migration in response to this growth factor.

Protein-tyrosine phosphatase activity of CD45 is activated by sequential phosphorylation by two kinases

1994 ◽  
Vol 14 (8) ◽  
pp. 5523-5532
Author(s):  
D R Stover ◽  
K A Walsh
Keyword(s):  
T Cell Activation ◽  
Protein Tyrosine Phosphatase ◽  
Time Course ◽  
Cell Activation ◽  
Regulatory Mechanism ◽  
Transmembrane Protein ◽  
Tyrosine Phosphatase ◽  
Protein Tyrosine

We describe a potential regulatory mechanism for the transmembrane protein-tyrosine phosphatase CD45. Phosphorylation on both tyrosine and serine residues in vitro results in an activation of CD45 specifically toward one artificial substrate but not another. The activation of these kinases appears to be order dependent, as it is enhanced when phosphorylation of tyrosine precedes that of serine but phosphorylation in the reverse order yields no activation. Any of four protein-tyrosine kinases tested, in combination with the protein-serine/threonine kinase, casein kinase II, was capable of mediating this activation in vitro. The time course of phosphorylation of CD45 in response to T-cell activation is consistent with the possibility that this regulatory mechanism is utilized in vivo.

scholarly journals Protein-tyrosine phosphatase activity of CD45 is activated by sequential phosphorylation by two kinases.

1994 ◽  
Vol 14 (8) ◽  
pp. 5523-5532 ◽  
Author(s):  
D R Stover ◽  
K A Walsh
Keyword(s):  
T Cell Activation ◽  
Protein Tyrosine Phosphatase ◽  
Time Course ◽  
Cell Activation ◽  
Regulatory Mechanism ◽  
Transmembrane Protein ◽  
Tyrosine Phosphatase ◽  
Protein Tyrosine

We describe a potential regulatory mechanism for the transmembrane protein-tyrosine phosphatase CD45. Phosphorylation on both tyrosine and serine residues in vitro results in an activation of CD45 specifically toward one artificial substrate but not another. The activation of these kinases appears to be order dependent, as it is enhanced when phosphorylation of tyrosine precedes that of serine but phosphorylation in the reverse order yields no activation. Any of four protein-tyrosine kinases tested, in combination with the protein-serine/threonine kinase, casein kinase II, was capable of mediating this activation in vitro. The time course of phosphorylation of CD45 in response to T-cell activation is consistent with the possibility that this regulatory mechanism is utilized in vivo.

scholarly journals Organization of F-Actin via Concerted Regulation of Kette by PTP61F and dAbl

2009 ◽  
Vol 29 (13) ◽  
pp. 3623-3632 ◽  
Author(s):  
Hsueh-Yen Ku ◽  
Chia-Lun Wu ◽  
Leonard Rabinow ◽  
Guang-Chao Chen ◽  
Tzu-Ching Meng
Keyword(s):  
Tyrosine Kinase ◽  
Tyrosine Phosphorylation ◽  
Protein Tyrosine Phosphatase ◽  
Actin Polymerization ◽  
Tyrosine Phosphatase ◽  
Phosphorylation Site ◽  
Actin Dynamics ◽  
S2 Cells ◽  
Actin Organization ◽  
First Time

ABSTRACT We identify Kette, a key regulator of actin polymerization, as a substrate for Drosophila protein tyrosine phosphatase PTP61F, as well as for dAbl tyrosine kinase. We further show that dAbl is a direct substrate for PTP61F. Therefore, Kette phosphotyrosine levels are regulated both directly and indirectly by PTP61F. Kette and PTP61F genetically interact in the regulation of F-actin organization in pupal eye discs, suggesting that tyrosine phosphorylation is essential for the proper regulation of Kette-mediated actin dynamics. This hypothesis was confirmed by demonstrating the loss of Kette-mediated F-actin organization and lamella formation in S2 cells in a Kette Y482F mutant in which the dAbl phosphorylation site was eliminated. Our results establish for the first time that PTP61F and dAbl ensure proper actin organization through the coordinated and reversible tyrosine phosphorylation of Kette.

scholarly journals Pyk2 phosphorylation of VE-PTP downstream of STIM1-induced Ca2+ entry regulates disassembly of adherens junctions

2017 ◽  
Vol 312 (6) ◽  
pp. L1003-L1017 ◽  
Author(s):  
Dheeraj Soni ◽  
Sushil C. Regmi ◽  
Dong-Mei Wang ◽  
Auditi DebRoy ◽  
You-Yang Zhao ◽  
...  
Keyword(s):  
Tyrosine Phosphorylation ◽  
Protein Tyrosine Phosphatase ◽  
Human Lung ◽  
Adherens Junctions ◽  
Tyrosine Phosphatase ◽  
Phosphorylation Site ◽  
Endothelial Permeability ◽  
Vascular Endothelial ◽  
Signaling Mechanism

Vascular endothelial protein tyrosine phosphatase (VE-PTP) stabilizes endothelial adherens junctions (AJs) through constitutive dephosphorylation of VE-cadherin. Here we investigated the role of stromal interaction molecule 1 (STIM1) activation of store-operated Ca2+ entry (SOCE) in regulating AJ assembly. We observed that SOCE induced by STIM1 activated Pyk2 in human lung microvascular endothelial cells (ECs) and induced tyrosine phosphorylation of VE-PTP at Y1981. Pyk2-induced tyrosine phosphorylation of VE-PTP promoted Src binding to VE-PTP, Src activation, and subsequent VE-cadherin phosphorylation and thereby increased the endothelial permeability response. The increase in permeability was secondary to disassembly of AJs. Pyk2-mediated responses were blocked in EC-restricted Stim1 knockout mice, indicating the requirement for STIM1 in initiating the signaling cascade. A peptide derived from the Pyk2 phosphorylation site on VE-PTP abolished the STIM1/SOCE-activated permeability response. Thus Pyk2 activation secondary to STIM1-induced SOCE causes tyrosine phosphorylation of VE-PTP, and VE-PTP, in turn, binds to and activates Src, thereby phosphorylating VE-cadherin to increase endothelial permeability through disassembly of AJs. Our results thus identify a novel signaling mechanism by which STIM1-induced Ca2+ signaling activates Pyk2 to inhibit the interaction of VE-PTP and VE-cadherin and hence increase endothelial permeability. Therefore, targeting the Pyk2 activation pathway may be a potentially important anti-inflammatory strategy.

Isolation and Identification of a Potent PTP1B Inhibitor, Ursolic Acid, from Carolina Jasmine (Gelsemium sempervirens (L.) J.St.-Hil.)

2020 ◽  
Vol 17 (12) ◽  
pp. 939-943
Author(s):  
Toshiro Noshita ◽  
Yusuke Kakizoe ◽  
Satoshi Tanabe ◽  
Hidekazu Ouchi ◽  
Akihiro Tai
Keyword(s):  
Ursolic Acid ◽  
Protein Tyrosine Phosphatase ◽  
Tyrosine Phosphatase ◽  
Active Agent ◽  
Protein Tyrosine Phosphatase 1B ◽  
Inhibiting Activity ◽  
Inhibition Activity ◽  
Isolation And Identification ◽  
Gelsemium Sempervirens

Extracts of Carolina jasmine (Gelsemium sempervirens (L.) J.St.-Hil.) petals were evaluated in vitro for inhibition activity against protein tyrosine phosphatase 1B (PTP1B). The principle active agent was also isolated from the extract and identified as ursolic acid (1). This is the first report of ursolic acid from G. sempervirens and of PTP1B-inhibiting activity in the genus Gelsemium.

scholarly journals PTPRD-inactivation-induced CXCL8 promotes angiogenesis and metastasis in gastric cancer and is inhibited by metformin

2019 ◽  
Vol 38 (1) ◽  
Author(s):  
Won Jung Bae ◽  
Ji Mi Ahn ◽  
Hye Eun Byeon ◽  
Seokwhi Kim ◽  
Dakeun Lee
Keyword(s):  
Microarray Analysis ◽  
Protein Tyrosine Phosphatase ◽  
Cancer Metastasis ◽  
Tyrosine Phosphatase ◽  
Underlying Mechanism ◽  
Tube Formation ◽  
Potential Therapeutic Target ◽  
Efficient Treatment ◽  
Stat3 Signaling

Abstract Background Protein tyrosine phosphatase receptor delta (PTPRD) is frequently inactivated in various types of cancers. Here, we explored the underlying mechanism of PTPRD-loss-induced cancer metastasis and investigated an efficient treatment option for PTPRD-inactivated gastric cancers (GCs). Methods PTPRD expression was evaluated by immunohistochemistry. Microarray analysis was used to identify differentially expressed genes in PTPRD-inactivated cancer cells. Quantitative reverse transcription (qRT-PCR), western blotting, and/or enzyme-linked immunosorbent assays were used to investigate the PTPRD-CXCL8 axis and the expression of other related genes. An in vitro tube formation assay was performed using HUVECs. The efficacy of metformin was assessed by MTS assay. Results PTPRD was frequently downregulated in GCs and the loss of PTPRD expression was associated with advanced stage, worse overall survival, and a higher risk of distant metastasis. Microarray analysis revealed a significant increase in CXCL8 expression upon loss of PTPRD. This was validated in various GC cell lines using transient and stable PTPRD knockdown. PTPRD-loss-induced angiogenesis was mediated by CXCL8, and the increase in CXCL8 expression was mediated by both ERK and STAT3 signaling. Thus, specific inhibitors targeting ERK or STAT3 abrogated the corresponding signaling nodes and inhibited PTPRD-loss-induced angiogenesis. Additionally, metformin was found to efficiently inhibit PTPRD-loss-induced angiogenesis, decrease cell viability in PTPRD-inactivated cancers, and reverse the decrease in PTPRD expression. Conclusions Thus, the PTPRD-CXCL8 axis may serve as a potential therapeutic target, particularly for the suppression of metastasis in PTPRD-inactivated GCs. Hence, we propose that the therapeutic efficacy of metformin in PTPRD-inactivated cancers should be further investigated.

Analysis of in vitro interactions of protein tyrosine phosphatase 1B with insulin receptors

2001 ◽  
Vol 173 (1-2) ◽  
pp. 109-120 ◽  
Author(s):  
Xin-Yuan Wang ◽  
Katrin Bergdahl ◽  
Anna Heijbel ◽  
Charlotta Liljebris ◽  
John E. Bleasdale
Keyword(s):  
Protein Tyrosine Phosphatase ◽  
Tyrosine Phosphatase ◽  
Insulin Receptors ◽  
Protein Tyrosine Phosphatase 1B ◽  
Protein Tyrosine ◽  
In Vitro Interactions
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