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• W2073252832 endingPage "2830" @default.
• W2073252832 startingPage "2817" @default.
• W2073252832 abstract "Many different types of cancer originate from aberrant signaling from the anaplastic lymphoma kinase (ALK) receptor tyrosine kinase (RTK), arising through different translocation events and overexpression. Further, activating point mutations in the ALK domain have been recently reported in neuroblastoma. To characterize signaling in the context of the full-length receptor, we have examined whether ALK is able to activate Rap1 and contribute to differentiation/proliferation processes. We show that ALK activates Rap1 via the Rap1-specific guanine-nucleotide exchange factor C3G, which binds in a constitutive complex with CrkL to activated ALK. The activation of the C3G/Rap1 pathway results in neurite outgrowth of PC12 cells, which is inhibited by either overexpression of Rap1GAP or siRNA-mediated knockdown of Rap1 itself or the guanine nucleotide exchange factor C3G. Significantly, this pathway also appears to function in the regulation of proliferation of neuroblastoma cells such as SK-N-SH and SH-SY5Y, because abrogation of Rap1 activity by Rap1-specific siRNA or overexpression of Rap1GAP reduces cellular growth. These results suggest that ALK activation of Rap1 may contribute to cell proliferation and oncogenesis of neuroblastoma driven by gain-of-function mutant ALK receptors." @default.
• W2073252832 created "2016-06-24" @default.
• W2073252832 creator A5001966222 @default.
• W2073252832 creator A5007977575 @default.
• W2073252832 creator A5044229149 @default.
• W2073252832 creator A5045216911 @default.
• W2073252832 creator A5067491040 @default.
• W2073252832 date "2010-03-01" @default.
• W2073252832 modified "2023-10-17" @default.
• W2073252832 title "Anaplastic lymphoma kinase activates the small GTPase Rap1 via the Rap1-specific GEF C3G in both neuroblastoma and PC12 cells" @default.
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• W2073252832 doi "https://doi.org/10.1038/onc.2010.27" @default.
• W2073252832 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/20190816" @default.
• W2073252832 hasPublicationYear "2010" @default.
• W2073252832 type Work @default.
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