دورية أكاديمية
أعرض في EDS

Soluble monomeric EphrinA1 is released from tumor cells and is a functional ligand for the EphA2 receptor.

التفاصيل البيبلوغرافية
العنوان: Soluble monomeric EphrinA1 is released from tumor cells and is a functional ligand for the EphA2 receptor.
المؤلفون: Wykosky J; Department of Neurosurgery, Brain Tumor Center of Excellence, Wake Forest University School of Medicine, Comprehensive Cancer Center, Winston-Salem, NC 27157, USA., Palma E, Gibo DM, Ringler S, Turner CP, Debinski W
المصدر: Oncogene [Oncogene] 2008 Dec 11; Vol. 27 (58), pp. 7260-73. Date of Electronic Publication: 2008 Sep 15.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Nature Publishing Group Country of Publication: England NLM ID: 8711562 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1476-5594 (Electronic) Linking ISSN: 09509232 NLM ISO Abbreviation: Oncogene Subsets: MEDLINE
أسماء مطبوعة: Publication: <2002->: Basingstoke : Nature Publishing Group
Original Publication: Basingstoke, Hampshire, UK : Scientific & Medical Division, MacMillan Press, c1987-
مواضيع طبية MeSH: Ephrin-A1/*metabolism , Glioblastoma/*metabolism , Receptor, EphA2/*metabolism, Biophysical Phenomena ; Cell Line, Tumor ; Ephrin-A1/chemistry ; Ephrin-A1/genetics ; Gene Expression Regulation ; Glioblastoma/genetics ; Humans ; Ligands ; Receptor, EphA2/genetics ; Solubility ; Transfection
مستخلص: The ephrinA1 ligand exerts antioncogenic effects in tumor cells through activation and downregulation of the EphA2 receptor and has been described as a membrane-anchored protein requiring clustering for function. However, while investigating the ephrinA1/EphA2 system in the pathobiology of glioblastoma multiforme (GBM), we uncovered that ephrinA1 is released from GBM and breast adenocarcinoma cells as a soluble, monomeric protein and is a functional form of the ligand in this state. Conditioned media containing a soluble monomer of ephrinA1 caused EphA2 internalization and downregulation, dramatic alteration of cell morphology and suppression of the Ras-MAPK pathway. Moreover, soluble monomeric ephrinA1 was functional in a physiological context, eliciting collapse of embryonic neuronal growth cones. We also found that ephrinA1 is cleaved from the plasma membrane of GBM cells, an event which involves the action of a metalloprotease. Thus, the ephrinA1 ligand can, indeed, function as a soluble monomer and may act in a paracrine manner on the EphA2 receptor without the need for juxtacrine interactions. These findings have important implications for further deciphering the function of these proteins in pathology and physiology, as well as for the design of ephrinA1-based EphA2-targeted antitumor therapeutics.
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معلومات مُعتمدة: F31 NS055533 United States NS NINDS NIH HHS; T32 CA113267 United States CA NCI NIH HHS; 5 T32 CA113267-04 United States CA NCI NIH HHS; 1 F31 NSO55533-01 United States PHS HHS
المشرفين على المادة: 0 (Ephrin-A1)
0 (Ligands)
EC 2.7.10.1 (Receptor, EphA2)
تواريخ الأحداث: Date Created: 20080917 Date Completed: 20090115 Latest Revision: 20211020
رمز التحديث: 20240628
مُعرف محوري في PubMed: PMC3683835
DOI: 10.1038/onc.2008.328
PMID: 18794797
قاعدة البيانات: MEDLINE
الوصف
تدمد:1476-5594
DOI:10.1038/onc.2008.328