scholarly journals HER Tyrosine Kinase Family and Rhabdomyosarcoma: Role in Onset and Targeted Therapy

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1808
Author(s):  
Carla De Giovanni ◽  
Lorena Landuzzi ◽  
Arianna Palladini ◽  
Giordano Nicoletti ◽  
Patrizia Nanni ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Tyrosine Kinases ◽  
Receptor Tyrosine Kinases ◽  
Myogenic Differentiation ◽  
Growth Factor Receptor ◽  
Her Family ◽  
Her2 Mutation ◽  
Epidermal Growth ◽  
Egfr Family

Rhabdomyosarcomas (RMS) are tumors of the skeletal muscle lineage. Two main features allow for distinction between subtypes: morphology and presence/absence of a translocation between the PAX3 (or PAX7) and FOXO1 genes. The two main subtypes are fusion-positive alveolar RMS (ARMS) and fusion-negative embryonal RMS (ERMS). This review will focus on the role of receptor tyrosine kinases of the human epidermal growth factor receptor (EGFR) family that is comprised EGFR itself, HER2, HER3 and HER4 in RMS onset and the potential therapeutic targeting of receptor tyrosine kinases. EGFR is highly expressed by ERMS tumors and cell lines, in some cases contributing to tumor growth. If not mutated, HER2 is not directly involved in control of RMS cell growth but can be expressed at significant levels. A minority of ERMS carries a HER2 mutation with driving activity on tumor growth. HER3 is frequently overexpressed by RMS and can play a role in the residual myogenic differentiation ability and in resistance to signaling-directed therapy. HER family members could be exploited for therapeutic approaches in two ways: blocking the HER member (playing a driving role for tumor growth with antibodies or inhibitors) and targeting expressed HER members to vehiculate toxins or immune effectors.

scholarly journals Receptor Tyrosine Kinases as Candidate Prognostic Biomarkers and Therapeutic Targets in Meningioma

2021 ◽  
Vol 22 (21) ◽  
pp. 11352
Author(s):  
Rafael Roesler ◽  
Barbara Kunzler Souza ◽  
Gustavo R. Isolan
Keyword(s):  
Tyrosine Kinases ◽  
Receptor Tyrosine Kinases ◽  
Therapeutic Targets ◽  
Growth Factor Receptor ◽  
Prognostic Biomarkers ◽  
Clinical Prognosis ◽  
Erbb Family ◽  
Cancer Types ◽  
Epidermal Growth

Meningioma (MGM) is the most common type of intracranial tumor in adults. The validation of novel prognostic biomarkers to better inform tumor stratification and clinical prognosis is urgently needed. Many molecular and cellular alterations have been described in MGM tumors over the past few years, providing a rational basis for the identification of biomarkers and therapeutic targets. The role of receptor tyrosine kinases (RTKs) as oncogenes, including those of the ErbB family of receptors, has been well established in several cancer types. Here, we review histological, molecular, and clinical evidence suggesting that RTKs, including the epidermal growth factor receptor (EGFR, ErbB1), as well as other members of the ErbB family, may be useful as biomarkers and therapeutic targets in MGM.

scholarly journals Quantifying the strength of heterointeractions among receptor tyrosine kinases from different subfamilies: Implications for cell signaling

2020 ◽  
Vol 295 (29) ◽  
pp. 9917-9933 ◽  
Author(s):  
Michael D. Paul ◽  
Hana N. Grubb ◽  
Kalina Hristova
Keyword(s):  
Growth Factor ◽  
Tyrosine Kinases ◽  
Receptor Tyrosine Kinases ◽  
Growth Factor Receptor ◽  
Vascular Endothelial ◽  
Eph Receptor ◽  
Vital Cell ◽  
Cell Processes ◽  
Epidermal Growth ◽  
Endothelial Growth Factor

Receptor tyrosine kinases (RTKs) are single-pass membrane proteins that control vital cell processes such as cell growth, survival, and differentiation. There is a growing body of evidence that RTKs from different subfamilies can interact and that these diverse interactions can have important biological consequences. However, these heterointeractions are often ignored, and their strengths are unknown. In this work, we studied the heterointeractions of nine RTK pairs, epidermal growth factor receptor (EGFR)–EPH receptor A2 (EPHA2), EGFR–vascular endothelial growth factor receptor 2 (VEGFR2), EPHA2–VEGFR2, EPHA2–fibroblast growth factor receptor 1 (FGFR1), EPHA2–FGFR2, EPHA2–FGFR3, VEGFR2–FGFR1, VEGFR2–FGFR2, and VEGFR2–FGFR3, using a FRET-based method. Surprisingly, we found that RTK heterodimerization and homodimerization strengths can be similar, underscoring the significance of RTK heterointeractions in signaling. We discuss how these heterointeractions can contribute to the complexity of RTK signal transduction, and we highlight the utility of quantitative FRET for probing multiple interactions in the plasma membrane.

Conformational Analysis of the Phosphorylated Epidermal Growth Factor Receptor

1999 ◽  
Vol 19 (5) ◽  
pp. 397-402 ◽  
Author(s):  
Anupam Bishayee ◽  
Laura Beguinot ◽  
Subal Bishayee
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Conformational Changes ◽  
Tyrosine Kinases ◽  
Egf Receptor ◽  
Receptor Tyrosine Kinases ◽  
Growth Factor Receptor ◽  
Tyrosine Residue ◽  
Peptide Antibody ◽  
Epidermal Growth

Phosphorylation-induced conformational changes have been well documented with different receptor tyrosine kinases. However, the susceptible epitopes and the tyrosine residue(s) involved in particular structural alteration mostly remain to be determined. Using a conformation-specific anti-peptide antibody, we have not only identified one such domain in the C-terminal tail of the EGF receptor but also identified the phosphate acceptor sites that are involved in the conformational change.

scholarly journals Role of receptor tyrosine kinases in G-protein-coupled receptor regulation of Ras: transactivation or parallel pathways?

2003 ◽  
Vol 376 (1) ◽  
pp. e9-e10 ◽  
Author(s):  
Julian DOWNWARD
Keyword(s):  
G Protein ◽  
Tyrosine Kinases ◽  
Receptor Tyrosine Kinases ◽  
Growth Factor Receptor ◽  
Nucleotide Exchange ◽  
Lpa Receptor ◽  
Ras Protein ◽  
Ras Activation ◽  
Epidermal Growth ◽  
G Protein Coupled

Ras protein regulation by G-protein-coupled receptors has been thought to occur through transactivation of receptor tyrosine kinases. New evidence suggests that these two receptor types independently control different pathways leading to Ras activation in response to lysophosphatidic acid (LPA). Epidermal growth factor receptor function is needed for basal nucleotide exchange on Ras, whereas the LPA receptor controls an inducible exchange activity.

scholarly journals Isatin-Hydrazones with Multiple Receptor Tyrosine Kinases (RTKs) Inhibitory Activity and In-Silico Binding Mechanism

2021 ◽  
Vol 11 (9) ◽  
pp. 3746
Author(s):  
Huda S. Al-Salem ◽  
Md Arifuzzaman ◽  
Iman S. Issa ◽  
A. F. M. Motiur Rahman
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Inhibitory Activity ◽  
Tyrosine Kinases ◽  
Receptor Tyrosine Kinases ◽  
Growth Factor Receptor ◽  
Competitive Inhibitors ◽  
Epidermal Growth ◽  
Multiple Receptor

Recently, we have reported a series of isatin hydrazone, two of them, namely, 3-((2,6-dichlorobenzylidene)hydrazono)indolin-2-one (1) and 3-((2-chloro-6-fluorobenzylidene)hydrazono)indolin-2-one (2) having potent cytotoxicity, showing cyclin-dependent kinases (CDK2) inhibitory activity and bearing recommended drug likeness properties. Since both compounds (1 and 2) showed inhibitory activity against CDK2, we assumed it would also have multiple receptor tyrosine kinases (RTKs) inhibitory activity. Considering those points, here, above-mentioned two isatin hydrazone 1 and 2 were synthesized using previously reported method for further investigation of their potency on RTKs (EGFR, VEGFR-2 and FLT-3) inhibitory activity. As expected, Compound 1 exhibited excellent inhibitory activity against epidermal growth factor receptor (EGFR, IC50 = 0.269 µM), vascular epidermal growth factor receptor 2 (VEGFR-2, IC50 = 0.232 µM) and FMS-like tyrosine kinase-3 (FLT-3, IC50 = 1.535 µM) tyrosine kinases. On the other hand, Compound 2 also exhibited excellent inhibitory activity against EGFR (IC50 = 0.369 µM), VEGFR-2 (IC50 = 0.266 µM) and FLT-3 (IC50 = 0.546 µM) tyrosine kinases. A molecular docking study with EGFR, VEGFR-2 and FLT-3 kinase suggested that both compounds act as type I ATP competitive inhibitors against EGFR and VEGFR-2, and type II ATP non-competitive inhibitors against FLT-3.

scholarly journals Role of ErbB/HER family of receptor tyrosine kinases in cholangiocyte biology

Hepatology ◽  
2017 ◽  
Vol 67 (2) ◽  
pp. 762-773 ◽  
Author(s):  
Anna Pellat ◽  
Javier Vaquero ◽  
Laura Fouassier
Keyword(s):  
Tyrosine Kinases ◽  
Receptor Tyrosine Kinases ◽  
Her Family
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