Tobacco Smoke Activates Protein Association and Tyrosine Phosphorylation of the GPI-Transamidase Complex Subunits in Human Cancers

Yiping Huang; Jatin Nagpal; Barry Trink; Edward Ratovitski

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Tobacco Smoke Activates Protein Association and Tyrosine Phosphorylation of the GPI-Transamidase Complex Subunits in Human Cancers

机译：烟草烟雾激活人类癌症中GPI-转酰胺酶复合物亚基的蛋白质缔合和酪氨酸磷酸化

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We previously found that the protein subunits of GPI-transamidase complex (e.g. PIG-U, PIG-T and GPAA1)play critical roles of oncogenes in human bladder and breast cancers manifesting their activities through signaling mechanismsthat involve urokinase receptor/Stat3 and paxillin pathways. We report here that cigarette smoke extract (CSE) enhancedcolony formation and invasiveness of certain human cancer cells (e.g. head and neck, bladder or breast). We foundthat CSE induced the complex formation between PIG-U, PIG-T and GPAA1 proteins and also the association betweenGPAA1 and EGFR in cancer cells. We observed that inhibitors of EGFR tyrosine kinase, Gefitinib or Erlotinib, modulatedtyrosine phosphorylation of PIG-U and PIG-T induced by CSE. We also found that EGFR tyrosine kinase inhibitorsand siRNA silencing of PIG-U, PIG-T or GPAA1 modulated the CSE-induced increase in colony formation and invasivenessof human bladder cancer cells. We suggest that the novel mechanism overlapping the oncogenic potential of PIG-U,PIG-T and GPAA1 implicates EGFR tyrosine phosphorylation of PIG-U or PIG-T and subsequent paxillin phosphorylation.

机译：我们先前发现，GPI-转酰胺酶复合物的蛋白亚基（例如PIG-U，PIG-T和GPAA1）在人类膀胱癌和乳腺癌中扮演着癌基因的关键角色，通过涉及尿激酶受体/ Stat3和paxillin途径的信号传导机制显示其活性。我们在此报告，香烟烟雾提取物（CSE）增强了某些人类癌细胞（例如头和颈部，膀胱或乳房）的菌落形成和侵袭性。我们发现，CSE诱导癌细胞中PIG-U，PIG-T和GPAA1蛋白之间的复杂形成，以及GPAA1和EGFR之间的关联。我们观察到EGFR酪氨酸激酶，吉非替尼或厄洛替尼的抑制剂可抑制CSE诱导的PIG-U和PIG-T的酪氨酸磷酸化。我们还发现，EGFR酪氨酸激酶抑制剂和PIG-U，PIG-T或GPAA1的siRNA沉默调节了CSE诱导的人膀胱癌细胞集落形成和侵袭性增加。我们建议，这种新颖的机制与PIG-U，PIG-T和GPAA1的致癌潜力重叠，牵涉到PIG-U或PIG-T的EGFR酪氨酸磷酸化以及随后的Paxillin磷酸化。

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《Journal of Epithelial Biology & Pharmacology》 |2009年第1期|共9页
作者
Yiping Huang; Jatin Nagpal; Barry Trink; Edward Ratovitski;
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中图分类细胞生物学;
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1. Activation of Epstein-Baff virus/C3d receptor (gp140, CR2, CD21) on human B lymphoma cell surface triggers Cb1 tyrosine phosphorylation, its association with p85 subunit, Crk-L and Syk and its dissociation with Vav [J] . Lottin-Divoux S, Jean D, Le Romancer M, Cellular Signalling . 2006,第8期

机译：在人B淋巴瘤细胞表面上激活爱泼斯坦-巴夫病毒/ C3d受体（gp140，CR2，CD21）会触发Cb1酪氨酸磷酸化，与p85亚基，Crk-L和Syk的缔合以及与Vav的解离
2. TNF-α Induces Tyrosine Phosphorylation and Recruitment of the Src Homology Protein-Tyrosine Phosphatase 2 to the gp130 Signal-Transducing Subunit of the IL-6 Receptor Complex [J] . Johannes G. Bode, Jens Schweigart, Jan Kehrmann, The journal of immunology . 2003,第1期

机译：TNF-α诱导酪氨酸磷酸化和Src同源蛋白酪氨酸磷酸酶2向IL-6受体复合物的gp130信号转导亚基的募集。
3. TNF-alpha Induces Tyrosine Phosphorylation and Recruitment of the Src Homology Protein-Tyrosine Phosphatase 2 to the gp130 Signal-Transducing Subunit of the IL-6 Receptor Complex. [J] . Bode JG, Schweigart J, Kehrmann J, The Journal of Immunology: Official Journal of the American Association of Immunologists . 2003,第1期

机译：TNF-α诱导酪氨酸磷酸化和Src同源性蛋白酪氨酸磷酸酶2到IL-6受体复合物的gp130信号转导亚基的募集。
4. Tyrosine phosphorylation of integrin-associated proteins in human macrophages as modulated by RGD and PHSRN domains [C] . W. John Kao, Yiping Liu Annual meeting of the Society For Biomaterials . 2003

机译：人巨噬细胞中整合素相关蛋白的酪氨酸磷酸化，受RGD和PHSRN结构域调节
5. Interaction of EphA2 with human cytoplasmic protein tyrosine phosphatase (HCPTP) variants and phosphorylation status of EphA2 in cancer cells by quantitative selected reaction monitoring mass spectrometry (SRM MS) [D] . Balasubramaniam, Deepa 2011

机译：EphA2与人胞浆蛋白酪氨酸磷酸酶（HCPTP）变体的相互作用以及癌细胞中EphA2的磷酸化状态的定量选择反应监测质谱（SRM MS）
6. Phosphorylation of the p34 subunit of human single-stranded-DNA-binding protein in cyclin A-activated G1 extracts is catalyzed by cdk-cyclin A complex and DNA-dependent protein kinase. [O] . Z Q Pan, A A Amin, E Gibbs, 1994

机译：cdk-cyclin A复合物和DNA依赖性蛋白激酶催化人单链DNA结合蛋白p34亚基在细胞周期蛋白A活化的G1提取物中的磷酸化。
7. Phosphorylation of the p34 subunit of human single-stranded-DNA-binding protein in cyclin A-activated G1 extracts is catalyzed by cdk-cyclin A complex and DNA-dependent protein kinase. [O] . Pan, Z Q, Amin, A A, Gibbs, E, 1994

机译：cdk-cyclin A复合物和依赖DNA的蛋白激酶催化人单链DNA结合蛋白p34亚基在细胞周期蛋白A活化的G1提取物中的磷酸化。
8. DMBA induces tyrosine phosphorylation of PLC-(gamma)1 and activates the tyrosine kinases lck and fyn in the HPB-ALL human T-cell line [R] . Archuleta, M M, Schieven, G L, Ledbetter, JA, 1993

机译：DmBa诱导pLC-（γ）1的酪氨酸磷酸化并激活HpB-aLL人T细胞系中的酪氨酸激酶lck和fyn。

Tobacco Smoke Activates Protein Association and Tyrosine Phosphorylation of the GPI-Transamidase Complex Subunits in Human Cancers

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