scholarly journals The Small 11-kDa Protein from B19 Parvovirus Binds Growth Factor Receptor-Binding Protein 2 in Vitro in a Src Homology 3 Domain/Ligand-Dependent Manner

Virology ◽  
2001 ◽  
Vol 291 (2) ◽  
pp. 285-291 ◽  
Author(s):  
Mannie M.Y. Fan ◽  
Lillian Tamburic ◽  
Cynthia Shippam-Brett ◽  
Darren B. Zagrodney ◽  
Caroline R. Astell
Keyword(s):  
Growth Factor ◽  
Receptor Binding ◽  
Growth Factor Receptor ◽  
Dependent Manner ◽  
Src Homology 3 ◽  
B19 Parvovirus ◽  
Src Homology 3 Domain ◽  
Src Homology ◽  
Receptor Binding Protein

scholarly journals Src Homology 3-Domain Growth Factor Receptor-Bound 2-Like (Endophilin) Interacting Protein 1, a Novel Neuronal Protein that Regulates Energy Balance

Endocrinology ◽  
2005 ◽  
Vol 146 (9) ◽  
pp. 3757-3764 ◽  
Author(s):  
James Trevaskis ◽  
Ken Walder ◽  
Victoria Foletta ◽  
Lyndal Kerr-Bayles ◽  
Janine McMillan ◽  
...  
Keyword(s):  
Body Weight ◽  
Growth Factor ◽  
Growth Factor Receptor ◽  
Domain Growth ◽  
Interacting Protein ◽  
Src Homology 3 ◽  
Src Homology 3 Domain ◽  
Src Homology ◽  
The Brain ◽  
Growth Factor Receptor Bound

Abstract To identify genes involved in the central regulation of energy balance, we compared hypothalamic mRNA from lean and obese Psammomys obesus, a polygenic model of obesity, using differential display PCR. One mRNA transcript was observed to be elevated in obese, and obese diabetic, P. obesus compared with lean animals and was subsequently found to be increased 4-fold in the hypothalamus of lethal yellow agouti (Ay/a) mice, a murine model of obesity and diabetes. Intracerebroventricular infusion of antisense oligonucleotide targeted to this transcript selectively suppressed its hypothalamic mRNA levels and resulted in loss of body weight in both P. obesus and Sprague Dawley rats. Reductions in body weight were mediated by profoundly reduced food intake without a concomitant reduction in metabolic rate. Yeast two-hybrid screening, and confirmation in mammalian cells by bioluminescence resonance energy transfer analysis, demonstrated that the protein it encodes interacts with endophilins, mediators of synaptic vesicle recycling and receptor endocytosis in the brain. We therefore named this transcript Src homology 3-domain growth factor receptor-bound 2-like (endophilin) interacting protein 1 (SGIP1). SGIP1 encodes a large proline-rich protein that is expressed predominantly in the brain and is highly conserved between species. Together these data suggest that SGIP1 is an important and novel member of the group of neuronal molecules required for the regulation of energy homeostasis.

The activation mechanism of ACK1 (activated Cdc42-associated tyrosine kinase 1)

2012 ◽  
Vol 445 (2) ◽  
pp. 255-264 ◽  
Author(s):  
Qiong Lin ◽  
Jian Wang ◽  
Chandra Childress ◽  
Wannian Yang
Keyword(s):  
Cell Adhesion ◽  
Growth Factor ◽  
Tyrosine Kinase ◽  
Molecular Mechanism ◽  
Growth Factor Receptor ◽  
Activation Mechanism ◽  
Src Homology 3 ◽  
Src Homology 3 Domain ◽  
Src Homology ◽  
Epidermal Growth

ACK [activated Cdc42 (cell division cycle 42)-associated tyrosine kinase; also called TNK2 (tyrosine kinase, non-receptor, 2)] is activated in response to multiple cellular signals, including cell adhesion, growth factor receptors and heterotrimeric G-protein-coupled receptor signalling. However, the molecular mechanism underlying activation of ACK remains largely unclear. In the present study, we demonstrated that interaction of the SH3 (Src homology 3) domain with the EBD [EGFR (epidermal growth factor receptor)-binding domain] in ACK1 forms an auto-inhibition of the kinase activity. Release of this auto-inhibition is a key step for activation of ACK1. Mutation of the SH3 domain caused activation of ACK1, independent of cell adhesion, suggesting that cell adhesion-mediated activation of ACK1 is through releasing the auto-inhibition. A region at the N-terminus of ACK1 (Leu10–Leu14) is essential for cell adhesion-mediated activation. In the activation of ACK1 by EGFR signalling, Grb2 (growth-factor-receptor-bound protein 2) mediates the interaction of ACK1 with EGFR through binding to the EBD and activates ACK1 by releasing the auto-inhibition. Furthermore, we found that mutation of Ser445 to proline caused constitutive activation of ACK1. Taken together, our studies have revealed a novel molecular mechanism underlying activation of ACK1.

scholarly journals Growth factor receptor binding protein 14 inhibition triggers insulin-induced mouse hepatocyte proliferation and is associated with hepatocellular carcinoma

Hepatology ◽  
2017 ◽  
Vol 65 (4) ◽  
pp. 1352-1368 ◽  
Author(s):  
Lucille Morzyglod ◽  
Michèle Caüzac ◽  
Lucie Popineau ◽  
Pierre-Damien Denechaud ◽  
Lluis Fajas ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Growth Factor ◽  
Receptor Binding ◽  
Binding Protein ◽  
Growth Factor Receptor ◽  
Hepatocyte Proliferation ◽  
Mouse Hepatocyte ◽  
Receptor Binding Protein

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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