Abstract:
:The binding of epidermal growth factor (EGF) to EGF receptor (EGFR) stimulates cell mitogenesis and survival through various signalling cascades. EGF also stimulates rapid EGFR endocytosis and its eventual degradation in lysosomes. The immediate events induced by ligand binding include receptor dimerization, activation of intrinsic tyrosine kinase and autophosphorylation. However, in spite of intensified efforts, the results regarding the roles of these events in EGFR signalling and internalization is still very controversial. In this study, we constructed a chimeric EGFR by replacing its extracellular domain with leucine zipper (LZ) and tagged a green fluorescent protein (GFP) at its C-terminus. We showed that the chimeric LZ-EGFR-GFP was constitutively dimerized. The LZ-EGFR-GFP dimer autophosphorylated each of its five well-defined C-terminal tyrosine residues as the ligand-induced EGFR dimer does. Phosphorylated LZ-EGFR-GFP was localized to both the plasma membrane and endosomes, suggesting it is capable of endocytosis. We also showed that LZ-EGFR-GFP activated major signalling proteins including Src homology collagen-like (Shc), extracellular signal-regulated kinase (ERK) and Akt. Moreover, LZ-EGFR-GFP was able to stimulate cell proliferation. These results indicate that non-ligand induced dimerization is sufficient to activate EGFR and initiate cell signalling and EGFR endocytosis. We conclude that receptor dimerization is a critical event in EGF-induced cell signalling and EGFR endocytosis.
journal_name
Int J Mol Scijournal_title
International journal of molecular sciencesauthors
Kourouniotis G,Wang Y,Pennock S,Chen X,Wang Zdoi
10.3390/ijms17081200subject
Has Abstractpub_date
2016-07-25 00:00:00issue
8issn
1422-0067pii
ijms17081200journal_volume
17pub_type
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journal_title:International journal of molecular sciences
pub_type: 杂志文章
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journal_title:International journal of molecular sciences
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journal_title:International journal of molecular sciences
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journal_title:International journal of molecular sciences
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journal_title:International journal of molecular sciences
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journal_title:International journal of molecular sciences
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journal_title:International journal of molecular sciences
pub_type: 杂志文章,评审
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journal_title:International journal of molecular sciences
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journal_title:International journal of molecular sciences
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journal_title:International journal of molecular sciences
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journal_title:International journal of molecular sciences
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journal_title:International journal of molecular sciences
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更新日期:2020-10-28 00:00:00
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journal_title:International journal of molecular sciences
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更新日期:2019-08-25 00:00:00
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journal_title:International journal of molecular sciences
pub_type: 杂志文章,评审
doi:10.3390/ijms19030921
更新日期:2018-03-20 00:00:00
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journal_title:International journal of molecular sciences
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更新日期:2019-01-29 00:00:00
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journal_title:International journal of molecular sciences
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journal_title:International journal of molecular sciences
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更新日期:2019-09-19 00:00:00
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journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms22010452
更新日期:2021-01-05 00:00:00