Disease relevance of NPY6R

• Finally, Sph-1-P-enhanced HUVEC motility, assessed by a phagokinetic assay using gold sol-coated plates and a Boyden's chamber assay, was markedly inhibited not only by pertussis toxin (or the Fyn kinase inhibitor PP2) but also by C3 exoenzyme (or Y-27632) [1].
• Human cytomegalovirus US28-mediated SMC migration is inhibited by treatment with PP2 and through the expression of either of two dominant negative inhibitors of FAK (F397Y and NH2-terminal amino acids 1-401) [2].
• In the current study, we determined the ability of PP2 (4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine), a Src kinase inhibitor, to reduce u-PAR expression and colon cancer invasion [3].
• After the spleens of severe combined immunodeficient mice were inoculated with cancer cells, treatment with PP2 for 3 weeks markedly reduced the rate of liver metastasis, compared with the control counterparts [4].
• Myocardial infarction rates per 1000 person-years were positively related to pulse pressure (PP1, 3.5; PP2, 2.9; PP3, 7.5; PP3 versus PP1, P = .02) [5].

High impact information on NPY6R

• Addition of the Lyn inhibitors PP2 and SU6656 to leukemic cell cultures restores cell apoptosis, and treatment of malignant cells with drugs that induce cell apoptosis decreases both activity and amount of the tyrosine kinase [6].
• In cardiac myocytes CVB3 activation of ERK-1/2 is blocked by the Src inhibitor PP2 [7].
• Transient anchorage was abolished by cholesterol depletion, addition of the Src family kinase (SFK) inhibitor PP2, or in Src-Yes-Fyn knockout cells [8].
• EphB1-mediated increase of cell migration was abrogated by the MEK inhibitor PD98059 and Src inhibitor PP2 [9].
• Consistent with these findings, infection studies show that PP2, a specific Src family kinase inhibitor, but not PP3, an inactive variant of this drug, reduces the ability of epithelial cells to support bacterial adhesion [10].

Chemical compound and disease context of NPY6R

• Capsaicin-induced currents in identified colonic dorsal root ganglion neurons were blocked by the c-Src kinase inhibitor PP2 and enhanced by the tyrosine phosphatase inhibitor sodium orthovandate [11].
• These in vitro findings provide a model by which a new tretinoin gel formulation containing PP-2 reduces irritation relative to a commercial tretinoin gel while maintaining clinical efficacy in the treatment of acne vulgaris [12].
• Finally, rottlerin and PP2 were both found to inhibit the growth of several glioblastoma cell lines, underscoring the potential of these agents to block glioblastoma growth [13].

Biological context of NPY6R

• Constitutively active Src increases GRK phosphorylation, whereas either expression of dominant-negative Src or treatment with the PP2 inhibitor abolishes tyrosine phosphorylation of GRK and desensitization [14].
• The mouse PP2 receptor expressed in COS cells binds rat 125I-PP with high affinity, i.e. IC50 = 65 pM [15].
• The coding region of the mouse PP2 gene reveals no introns and predicts a seven transmembrane domain (TM) receptor of 371 amino acids [15].
• We have also cloned the human homologue of PP2, which is a single copy gene and maps to human chromosome 5q31 [15].
• However, a 9.8-kb PP2 transcript was detectable in 7-day-old mouse embryo, i.e. prior to the organogenesis of pancreas and the onset of PP production [15].

Anatomical context of NPY6R

• Polyclonal antibodies raised against pumpkin phloem exudate were used to isolate several cDNAs corresponding to PP1 and PP2 [16].
• We report here that a src family tyrosine kinase-specific inhibitor, PP2, enhances neurotransmitter release from PC12 cells and primary cultured neurons [17].
• These events seem to be mediated by Src-like catalyzed phosphorylation of band 3 because both SHP-2 translocation to cellular membranes and its interaction with Tyr-phosphorylated protein are greatly counteracted by PP2, a specific inhibitor of Src kinases [18].
• Each of the stable cell lines in which kinase-defective mutants of c-Src were expressed had reduced levels of Bcl-x(L.) However, inhibition of c-Src kinase activity by PP2 in vector control cells did not alter the oxaliplatin response over 72 h nor did it reduce Bcl-x(L) levels [19].
• In contrast, the injury of endothelial cells mediated by H(2)O(2) is inhibited by PP2, a selective specific inhibitor for protein-tyrosine kinase Src [20].

Associations of NPY6R with chemical compounds

• The PP2 mRNA was localized within the phloem of pumpkin hypocotyl cross-sections based on in situ hybridization of a digoxigenin-labeled antisense probe [16].
• IL-1beta-mediated hyperpolarization is blocked by PP2, the selective inhibitor of the protein tyrosine kinase Src, which is known to be activated by ceramide [21].
• In contrast, ERK activation was insensitive to PP2 and piceatannol [22].
• Costimulation of G(i) plus G(z) pathways also caused thromboxane generation that was dependent on outside-in signaling and was inhibited by PP2, a Src family tyrosine kinase inhibitor [23].
• Mutation of Nrf2Y568 to phenylalanine and src kinase inhibitor PP2 abrogated/reduced the UVB-induced phosphorylation of Nrf2Y568 and nuclear exclusion of Nrf2 [24].

Analytical, diagnostic and therapeutic context of NPY6R

• Sequence analysis of PP2 cDNAs revealed a 654-bp open reading frame encoding a 218-amino acid polypeptide; this polypeptide had the carbohydrate binding characteristics of a PP2 subunit [16].
• Dual immunofluorescence labeling of the P2Y(2) receptor and the EGFR indicated that UTP caused an increase in the co-localization of these receptors in the plasma membrane that was prevented by the Src inhibitor PP2 [25].
• EXPERIMENTAL DESIGN: Western blotting, Northern blotting, and u-PAR promoter-reporter assays were performed to determine whether PP2 represses u-PAR expression [3].
• Electron microscopy further revealed that PP2-treated WNV-infected cells accumulated an increased number of virions in the ER compared to untreated cells [26].
• The Tyr701 phosphorylation of signal transducer and activator of transcription 1 (STAT1) induced by interferon-gamma (IFN-gamma) and 12-O-tetradecanoylphorbol 13-acetate (TPA) was inhibited by the protein kinase C (PKC) inhibitor staurosporine, the tyrosine kinase inhibitor herbimycin, or the Src kinase inhibitor PP2 [27].

References