scholarly journals ErBb Family Proteins in Cholangiocarcinoma and Clinical Implications

2020 ◽  
Vol 9 (7) ◽  
pp. 2255
Author(s):  
Wook Jin
Keyword(s):  
Cellular Networks ◽  
Tyrosine Kinases ◽  
Receptor Tyrosine Kinases ◽  
Growth Factor Receptor ◽  
Clinical Implications ◽  
Tumor Aggressiveness ◽  
Erbb Family ◽  
Constitutive Activation ◽  
Epidermal Growth ◽  
Viral Oncogene Homolog

The erythroblastic leukemia viral oncogene homolog (ErBb) family consists of the receptor tyrosine kinases (RTK) epidermal growth factor receptor (EGFR; also called ERBB1), ERBB2, ERBB3, and ERBB4. This family is closely associated with the progression of cholangiocarcinoma (CC) through the regulation of cellular networks, which are enhanced during tumorigenesis, metastasis, and chemoresistance. Additionally, the constitutive activation of cellular signaling by the overexpression and somatic mutation-mediated alterations conferred by the ErBb family on cholangiocarcinoma and other cancers enhances tumor aggressiveness and chemoresistance by contributing to the tumor microenvironment. This review summarizes the recent findings on the molecular functions of the ErBb family and their mutations during the progression of cholangiocarcinoma. It also discusses the developments and applications of various devising strategies for targeting the ErBb family through different inhibitors in various stages of clinical trials, which are essential for improving targeted clinical therapies.

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 Receptor Tyrosine Kinases as Candidate Prognostic Biomarkers in Meningioma

2021 ◽  
Author(s):  
Rafael Roesler ◽  
Barbara Kunzler Souza ◽  
Gustavo R. Isolan
Keyword(s):  
Tyrosine Kinases ◽  
Clinical Evidence ◽  
Growth Factor Receptor ◽  
Prognostic Biomarkers ◽  
Clinical Prognosis ◽  
Erbb Family ◽  
The Past ◽  
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 kinase (RTKs), including those of the ErbB family of receptors, as oncogenes 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, ErbB 1), as well as other members of the ErbB family, may be useful as biomarkers in MGM.

Sign in / Sign up

Export Citation Format

Share Document