A nuclear protein is required for thyroid hormone receptor binding to an inhibitory half-site in the epidermal growth factor receptor promoter

1992 ◽  
Vol 6 (4) ◽  
pp. 627-635 ◽  
Author(s):  
K. L. Thompson
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Thyroid Hormone ◽  
Epidermal Growth Factor ◽  
Receptor Binding ◽  
Nuclear Protein ◽  
Thyroid Hormone Receptor ◽  
Growth Factor Receptor ◽  
Epidermal Growth ◽  
Half Site

scholarly journals Growth Factor Receptor Binding Protein 2-mediated Recruitment of the RING Domain of Cbl to the Epidermal Growth Factor Receptor Is Essential and Sufficient to Support Receptor Endocytosis

2005 ◽  
Vol 16 (3) ◽  
pp. 1268-1281 ◽  
Author(s):  
Fangtian Huang ◽  
Alexander Sorkin
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Receptor Binding ◽  
Binding Protein ◽  
Growth Factor Receptor ◽  
Ring Domain ◽  
Receptor Endocytosis ◽  
Epidermal Growth ◽  
Receptor Binding Protein

Knockdown of growth factor receptor binding protein 2 (Grb2) by RNA interference strongly inhibits clathrin-mediated endocytosis of the epidermal growth factor receptor (EGFR). To gain insights into the function of Grb2 in EGFR endocytosis, we have generated cell lines in which endogenous Grb2 was replaced by yellow fluorescent protein (YFP)-tagged Grb2 expressed at the physiological level. In these cells, Grb2-YFP fully reversed the inhibitory effect of Grb2 knockdown on EGFR endocytosis and, moreover, trafficked together with EGFR during endocytosis. Overexpression of Grb2-binding protein c-Cbl did not restore endocytosis in Grb2-depleted cells. However, EGFR endocytosis was rescued in Grb2-depleted cells by chimeric proteins consisting of the Src homology (SH) 2 domain of Grb2 fused to c-Cbl. The “knockdown and rescue” analysis revealed that the expression of Cbl-Grb2/SH2 fusions containing RING finger domain of Cbl restores normal ubiquitylation and internalization of the EGFR in the absence of Grb2, consistent with the important role of the RING domain in EGFR endocytosis. In contrast, the carboxy-terminal domain of Cbl, when attached to Grb2 SH2 domain, had 4 times smaller endocytosis-rescue effect compared with the RING-containing chimeras. Together, the data suggest that the interaction of Cbl carboxy terminus with CIN85 has a minor and a redundant role in EGFR internalization. We concluded that Grb2-mediated recruitment of the functional RING domain of Cbl to the EGFR is essential and sufficient to support receptor endocytosis.

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