کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2151327 | 1089982 | 2013 | 18 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Molecular and Functional Characterizations of the Association and Interactions between Nucleophosmin-Anaplastic Lymphoma Kinase and Type I Insulin-Like Growth Factor Receptor
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کلمات کلیدی
type I insulin-like growth factor receptorPLANPMGSTPLC-γIGF-IRCHXPDGFRFBSProximity ligation assay - آزمون لمس نزدیکیALK - آلکImmunoprecipitation - تخریب ایمنیfetal bovine serum - سرم جنین گاوcycloheximide - سیکلوهایسیمیدphospholipase C-γ - فسفولیپاز C-γAnaplastic lymphoma kinase - لنفوم کیناز Anaplasticwild type - نوع وحشیnucleophosmin - نوکلئوفسمیWestern blot - وسترن بلاتglutathione S-transferase - گلوتاتیون S-ترانسفرازplatelet-derived growth factor receptor - گیرنده عامل فاکتور رشد یافته پلاکت
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
تحقیقات سرطان
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Molecular and Functional Characterizations of the Association and Interactions between Nucleophosmin-Anaplastic Lymphoma Kinase and Type I Insulin-Like Growth Factor Receptor Molecular and Functional Characterizations of the Association and Interactions between Nucleophosmin-Anaplastic Lymphoma Kinase and Type I Insulin-Like Growth Factor Receptor](/preview/png/2151327.png)
چکیده انگلیسی
Nucleophosmin-anaplastic lymphoma kinase (NPM-ALK) is aberrantly expressed in a subset of T cell lymphoma that commonly affects children and young adults. NPM-ALK possesses significant oncogenic potential that was previously documented using in vitro and in vivo experimental models. The exact mechanisms by which NPM-ALK induces its effects are poorly understood. We have recently demonstrated that NPM-ALK is physically associated with type I insulin-like growth factor receptor (IGF-IR). A positive feedback loop appears to exist between NPM-ALK and IGF-IR through which these two kinases interact to potentiate their effects. We have also found that a single mutation of the Tyr644 or Tyr664 residue of the C terminus of NPM-ALK to phenylalanine decreases significantly, but does not completely abolish, the association between NPM-ALK and IGF-IR. The purpose of this study was to determine whether the dual mutation of Tyr644 and Tyr664 abrogates the association and interactions between NPM-ALK and IGF-IR. We also examined the impact of this dual mutation on the oncogenic potential of NPM-ALK. Our results show that NPM-ALKY644,664F completely lacks association with IGF-IR. Importantly, we found that the dual mutation of Tyr644 and Tyr664 diminishes the oncogenic effects of NPM-ALK, including its ability to induce anchorage-independent colony formation and to sustain cellular transformation, proliferation, and migration. Furthermore, the association between NPM-ALK and IGF-IR through Tyr644 and Tyr664 appears to contribute to maintaining the stability of NPM-ALK protein. Our results provide novel insights into the mechanisms by which NPM-ALK induces its oncogenic effects through interactions with IGF-IR in this aggressive lymphoma.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neoplasia - Volume 15, Issue 6, June 2013, Pages 669-683, IN22-IN24
Journal: Neoplasia - Volume 15, Issue 6, June 2013, Pages 669-683, IN22-IN24
نویسندگان
Bin Shi, Deeksha Vishwamitra, J. Gabrielle Granda, Thomas Whitton, Ping Shi, Hesham M Amin,