Selectivity and Mechanism of Action of a Growth Factor Receptor-Bound Protein 2 Src Homology 2 Domain Binding Antagonist

Alessio Giubellino; Zhen-Dan Shi; Lisa M. Miller Jenkins; Karen M. Worthy; Lakshman K. Bindu; Gagani Athauda; Benedetta Peruzzi; Robert J. Fisher; Ettore Appella; Terrence R. Burke; Donald P. Bottaro

doi:10.1021/jm800523u

Selectivity and Mechanism of Action of a Growth Factor Receptor-Bound Protein 2 Src Homology 2 Domain Binding Antagonist

Journal of Medicinal Chemistry ◽

10.1021/jm800523u ◽

2008 ◽

Vol 51 (23) ◽

pp. 7459-7468 ◽

Cited By ~ 7

Author(s):

Alessio Giubellino ◽

Zhen-Dan Shi ◽

Lisa M. Miller Jenkins ◽

Karen M. Worthy ◽

Lakshman K. Bindu ◽

...

Keyword(s):

Growth Factor ◽

Mechanism Of Action ◽

Growth Factor Receptor ◽

Src Homology 2 ◽

Src Homology ◽

Src Homology 2 Domain ◽

Growth Factor Receptor Bound

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Nuclear Magnetic Resonance Solution Structure of the Growth Factor Receptor-Bound Protein 2 Src Homology 2 Domain

Biochemistry ◽

10.1021/bi952615s ◽

1996 ◽

Vol 35 (36) ◽

pp. 11852-11864 ◽

Cited By ~ 12

Author(s):

Kevin H. Thornton ◽

W. Tom Mueller ◽

Patrick McConnell ◽

Guochang Zhu ◽

Alan R. Saltiel ◽

...

Keyword(s):

Nuclear Magnetic Resonance ◽

Growth Factor ◽

Magnetic Resonance ◽

Solution Structure ◽

Growth Factor Receptor ◽

Src Homology 2 ◽

Resonance Solution ◽

Src Homology ◽

Src Homology 2 Domain ◽

Growth Factor Receptor Bound

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p66shc Negatively Regulates Insulin-Like Growth Factor I Signal Transduction via Inhibition of p52shc Binding to Src Homology 2 Domain-Containing Protein Tyrosine Phosphatase Substrate-1 Leading to Impaired Growth Factor Receptor-Bound Protein-2 Membrane Recruitment

Molecular Endocrinology ◽

10.1210/me.2008-0079 ◽

2008 ◽

Vol 22 (9) ◽

pp. 2162-2175 ◽

Cited By ~ 37

Author(s):

Gang Xi ◽

Xinchun Shen ◽

David R. Clemmons

Keyword(s):

Growth Factor ◽

Protein Tyrosine Phosphatase ◽

Tyrosine Phosphatase ◽

Growth Factor Receptor ◽

Membrane Recruitment ◽

Factor I ◽

Src Homology 2 ◽

Src Homology ◽

Src Homology 2 Domain ◽

Growth Factor Receptor Bound

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Inhibition of Tumor Metastasis by a Growth Factor Receptor Bound Protein 2 Src Homology 2 Domain–Binding Antagonist

Cancer Research ◽

10.1158/0008-5472.can-07-0022 ◽

2007 ◽

Vol 67 (13) ◽

pp. 6012-6016 ◽

Cited By ~ 29

Author(s):

Alessio Giubellino ◽

Yang Gao ◽

Sunmin Lee ◽

Min-Jung Lee ◽

James R. Vasselli ◽

...

Keyword(s):

Growth Factor ◽

Tumor Metastasis ◽

Growth Factor Receptor ◽

Src Homology 2 ◽

Src Homology ◽

Src Homology 2 Domain ◽

Growth Factor Receptor Bound

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Development of Non-Peptide Ligands of Growth Factor Receptor-Bound Protein 2-Src Homology 2 Domain Using Molecular Modeling and NMR Spectroscopy†

Journal of Medicinal Chemistry ◽

10.1021/jm101478n ◽

2011 ◽

Vol 54 (4) ◽

pp. 1096-1100 ◽

Cited By ~ 5

Author(s):

Ángel L. Orcajo-Rincón ◽

Silvia Ortega-Gutiérrez ◽

Pedro Serrano ◽

Ivan R. Torrecillas ◽

Kurt Wüthrich ◽

...

Keyword(s):

Molecular Modeling ◽

Nmr Spectroscopy ◽

Growth Factor ◽

Growth Factor Receptor ◽

Peptide Ligands ◽

Src Homology 2 ◽

Src Homology ◽

Src Homology 2 Domain ◽

Growth Factor Receptor Bound

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Growth Factor Receptor-bound Protein 2 Interaction with the Tyrosine-phosphorylated Tail of Amyloid β Precursor Protein Is Mediated by Its Src Homology 2 Domain

Journal of Biological Chemistry ◽

10.1074/jbc.m400488200 ◽

2004 ◽

Vol 279 (24) ◽

pp. 25374-25380 ◽

Cited By ~ 33

Author(s):

Dawang Zhou ◽

Cristiana Noviello ◽

Chiara D'Ambrosio ◽

Andrea Scaloni ◽

Luciano D'Adamio

Keyword(s):

Growth Factor ◽

Growth Factor Receptor ◽

Amyloid Β ◽

Precursor Protein ◽

Src Homology 2 ◽

Src Homology ◽

Src Homology 2 Domain ◽

Growth Factor Receptor Bound

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Direct analysis of the binding of the abl Src homology 2 domain to the activated epidermal growth factor receptor.

Journal of Biological Chemistry ◽

10.1016/s0021-9258(18)53920-x ◽

1993 ◽

Vol 268 (3) ◽

pp. 1775-1779 ◽

Cited By ~ 1

Author(s):

G. Zhu ◽

S.J. Decker ◽

B.J. Mayer ◽

A.R. Saltiel

Keyword(s):

Epidermal Growth Factor Receptor ◽

Growth Factor ◽

Epidermal Growth Factor ◽

Growth Factor Receptor ◽

Direct Analysis ◽

Src Homology 2 ◽

Src Homology ◽

Epidermal Growth ◽

Src Homology 2 Domain

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The Src Homology 2 Domain of Rin1 Mediates Its Binding to the Epidermal Growth Factor Receptor and Regulates Receptor Endocytosis

Journal of Biological Chemistry ◽

10.1074/jbc.m304324200 ◽

2003 ◽

Vol 278 (34) ◽

pp. 32027-32036 ◽

Cited By ~ 65

Author(s):

M. Alejandro Barbieri ◽

Chen Kong ◽

Pin-I Chen ◽

Bruce F. Horazdovsky ◽

Philip D. Stahl

Keyword(s):

Epidermal Growth Factor Receptor ◽

Growth Factor ◽

Epidermal Growth Factor ◽

Growth Factor Receptor ◽

Receptor Endocytosis ◽

Src Homology 2 ◽

Src Homology ◽

Epidermal Growth ◽

Src Homology 2 Domain

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Design and Synthesis of 4-(α-Hydroxymalonyl)phenylalanine as a New Phosphotyrosyl Mimetic and Its Use in Growth Factor Receptor Bound 2 Src-Homology 2 (Grb2 SH2) Domain-Binding Peptides

Journal of Medicinal Chemistry ◽

10.1021/jm050154v ◽

2005 ◽

Vol 48 (16) ◽

pp. 5369-5372 ◽

Cited By ~ 5

Author(s):

Sang-Uk Kang ◽

Karen M. Worthy ◽

Lakshman K. Bindu ◽

Manchao Zhang ◽

Dajun Yang ◽

...

Keyword(s):

Growth Factor ◽

Growth Factor Receptor ◽

Sh2 Domain ◽

Design And Synthesis ◽

Src Homology 2 ◽

Src Homology ◽

Binding Peptides ◽

Growth Factor Receptor Bound

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Affinity chromatography for purification of the modular protein growth factor receptor-bound protein 2 and development of a screening test for growth factor receptor-bound protein 2 Src homology 3 domain inhibitor using peroxidase-linked ligand

Analytical Biochemistry ◽

10.1016/j.ab.2005.12.032 ◽

2006 ◽

Vol 351 (1) ◽

pp. 93-99 ◽

Cited By ~ 2

Author(s):

B. Gril ◽

W.Q. Liu ◽

C. Lenoir ◽

C. Garbay ◽

M. Vidal

Keyword(s):

Growth Factor ◽

Affinity Chromatography ◽

Screening Test ◽

Growth Factor Receptor ◽

Src Homology 3 ◽

Src Homology 3 Domain ◽

Src Homology ◽

Growth Factor Receptor Bound

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SRC-homology 2 domain-containing phosphatase 2 (SHP2) in epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma (LUAD).

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.9540 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. 9540-9540

Author(s):

Rafael Rosell ◽

Masaoki Ito ◽

Jordi Codony-Servat ◽

Ana Giménez-Capitán ◽

Mireia Serra-Mitjans ◽

...

Keyword(s):

Growth Factor ◽

Epidermal Growth Factor ◽

Mrna Expression ◽

Mrna Levels ◽

Wild Type ◽

Src Homology 2 ◽

Src Homology ◽

Epidermal Growth ◽

Src Homology 2 Domain ◽

Egfr Mutant

9540 Background: Epidermal growth factor (EGFR)-mutant lung adenocarcinomas (LUADs) display impaired phosphorylation of extracellular signal-regulated kinase (ERK) and SRC-homology 2 domain-containing phosphatase 2 (SHP2) in comparison with EGFR wild-type LUADs. However, the function of SHP2 in early EGFR-mutant LUADs and EGFR wild-type LUADs has not been reported. We posit that SHP2 mRNA expression could be a predictive marker in resected EGFR-mutant LUADs versus EGFR wild-type patients (pts). Methods: We examined 267 resected LUADs from Japan and Spain. mRNA expression levels of AXL, MET, CDCP1, STAT3, YAP1 and SHP2 were analyzed by quantitative reverse transcriptase polymerase chain reaction (PCR). EGFR mutant cell lines were investigated for their activity of SHP2. Results: Among the 267 enrolled pts, 100 (37.3%) were EGFR-mutant LUADs. Five-year recurrence-free survival (RFS) and overall survival (OS) were lower for EGFR-mutant LUADs with high SHP2 mRNA levels (hazard ratio = 1.83 and 2.28, respectively. p = 0.03 and p = 0.04). However, SHP2 was not associated with RFS nor OS in the 167 wild-type EGFR LUADs. In EGFR-mutant cells, RMC-4550 (SHP2 inhibitor) plus erlotinib showed synergism via inhibition of AKT (S473) and ERK1/2 (T202/Y204). While erlotinib translocates SHP2 (Y542) into the nucleus, either RMC-4550 alone, or in combination with erlotinib, relocalizes SHP2 into the cytoplasm membrane, limiting AKT and ERK activation. Conclusions: High SHP2 mRNA is related to shorter RFS and OS in EGFR-mutant LUADs, but not in EGFR wild-type LUADs. The findings indicate that the addition of SHP2 inhibitors could improve adjuvant therapy in EGFR-mutant LUADs.

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