Transmembrane signalling pathways initiating cell growth in fibroblasts

1988 ◽  
Vol 320 (1199) ◽  
pp. 427-436 ◽  
Keyword(s):  
Growth Factor ◽  
Cell Line ◽  
Tyrosine Kinases ◽  
Receptor Tyrosine Kinases ◽  
Growth Arrest ◽  
Chinese Hamster ◽  
Signalling Pathways ◽  
Fibroblastic Cell ◽  
Growth Factor Signalling ◽  
Growth Factor Signalling Pathway

The mechanisms of growth factor action were studied in a fibroblastic cell line capable of reversible growth arrest in G0-G1. This cell line, derived from Chinese hamster lung, can be stimulated to divide by a limited set of purified growth factors, including EGF, FGF, PDGF, x-thrombin (THR), serotonin (5-HT) and insulin. THR and 5-HT stimulate, via a G-protein (G p ), a polyphosphoinositide-specific phospholipase C (PtdIns(4,5)P 2 -PLC). In contrast, the mitogens EGF, FGF, PDGF, and insulin do not stimulate PtdIns(4,5)P 2 -PLC, unless this pathway has been preactivated by THR or AIF 4 . Finally, from the specific inhibitory action of pertussis toxin on THR- and 5-HT-induced DNA synthesis, and from the exploitation of the 5-HT pharmacological tools, we conclude that: (i) there are at least two distinct Gproteins involved in signalling growth: G p , coupling receptors to PtdIns(4,5)P 2 -PLC, and G 1 coupling receptors negatively to adenylyl cyclase and probably to other unknown effector(s); (ii) activation of receptor-tyrosine kinases provides an alternate growth factor signalling pathway, independent of G p - and G i -mediated actions; and (iii) tyrosine kinases positively ‘cross-communicate ’ with the inositol-lipid pathway (phosphorylation of G p , PLC, Ptdlns kinases...?).

Growth factors and associated signalling pathways in tumour progression and in cancer treatment

2019 ◽  
pp. 105-122
Author(s):  
Nadège Gaborit ◽  
Yosef Yarden
Keyword(s):  
Growth Factors ◽  
Tyrosine Kinases ◽  
Normal Tissue ◽  
Receptor Tyrosine Kinases ◽  
Tumour Progression ◽  
Signalling Pathways ◽  
Polypeptide Growth Factors ◽  
Growth Factor Signalling ◽  
Approved Drugs ◽  
Nuclear Alterations

To gain increased proliferation, blood supply, invasiveness, and resistance to cytotoxic treatments, cancer cells continuously secrete polypeptide growth factors, or they utilize factors produced by the associated normal tissue and the immunological microenvironment. The growth factors relay biochemical messages by binding with receptor tyrosine kinases (RTKs) located at the cell surface. In response to activation and receptor auto-phosphorylation, RTKs mobilize diverse signalling pathways, which culminate in cytoplasmic and nuclear alterations, including activation of gene expression programmes. This chapter describes several well-characterized growth factors, highlights the cognate receptors and downstream signalling pathways, and exemplifies involvement of specific growth factors in maintenance of the hallmarks of cancer. An account of clinically approved drugs able to intercept growth factor signalling closes this chapter.

Growth factors and associated signalling pathways in tumour progression and in cancer treatment

2019 ◽  
pp. 105-122
Author(s):  
Nadège Gaborit ◽  
Yosef Yarden
Keyword(s):  
Growth Factors ◽  
Tyrosine Kinases ◽  
Normal Tissue ◽  
Receptor Tyrosine Kinases ◽  
Tumour Progression ◽  
Signalling Pathways ◽  
Polypeptide Growth Factors ◽  
Growth Factor Signalling ◽  
Approved Drugs ◽  
Nuclear Alterations

To gain increased proliferation, blood supply, invasiveness, and resistance to cytotoxic treatments, cancer cells continuously secrete polypeptide growth factors, or they utilize factors produced by the associated normal tissue and the immunological microenvironment. The growth factors relay biochemical messages by binding with receptor tyrosine kinases (RTKs) located at the cell surface. In response to activation and receptor auto-phosphorylation, RTKs mobilize diverse signalling pathways, which culminate in cytoplasmic and nuclear alterations, including activation of gene expression programmes. This chapter describes several well-characterized growth factors, highlights the cognate receptors and downstream signalling pathways, and exemplifies involvement of specific growth factors in maintenance of the hallmarks of cancer. An account of clinically approved drugs able to intercept growth factor signalling closes this chapter.

scholarly journals Comparison of growth factor signalling pathway utilisation in cultured normal melanocytes and melanoma cell lines

BMC Cancer ◽  
2012 ◽  
Vol 12 (1) ◽  
Author(s):  
Ji Eun Kim ◽  
Clare Stones ◽  
Wayne R Joseph ◽  
Euphemia Leung ◽  
Graeme J Finlay ◽  
...  
Keyword(s):  
Growth Factor ◽  
Cell Lines ◽  
Melanoma Cell ◽  
Signalling Pathway ◽  
Growth Factor Signalling ◽  
Melanoma Cell Lines ◽  
Growth Factor Signalling Pathway

scholarly journals Exploring the Gamut of Receptor Tyrosine Kinases for Their Promise in the Management of Non-Alcoholic Fatty Liver Disease

Biomedicines ◽  
2021 ◽  
Vol 9 (12) ◽  
pp. 1776
Author(s):  
Sayali Bhave ◽  
Han Kiat Ho
Keyword(s):  
Growth Factor ◽  
Tyrosine Kinases ◽  
Fatty Liver Disease ◽  
Drug Targets ◽  
Fibroblast Growth Factor Receptor ◽  
Receptor Tyrosine Kinases ◽  
Growth Factor Receptor ◽  
Fibroblast Growth ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

Recently, non-alcoholic fatty liver disease (NAFLD) has emerged as a predominant health concern affecting approximately a quarter of the world’s population. NAFLD is a spectrum of liver ailments arising from nascent lipid accumulation and leading to inflammation, fibrosis or even carcinogenesis. Despite its prevalence and severity, no targeted pharmacological intervention is approved to date. Thus, it is imperative to identify suitable drug targets critical to the development and progression of NAFLD. In this quest, a ray of hope is nestled within a group of proteins, receptor tyrosine kinases (RTKs), as targets to contain or even reverse NAFLD. RTKs control numerous vital biological processes and their selective expression and activity in specific diseases have rendered them useful as drug targets. In this review, we discuss the recent advancements in characterizing the role of RTKs in NAFLD progression and qualify their suitability as pharmacological targets. Available data suggests inhibition of Epidermal Growth Factor Receptor, AXL, Fibroblast Growth Factor Receptor 4 and Vascular Endothelial Growth Factor Receptor, and activation of cellular mesenchymal-epithelial transition factor and Fibroblast Growth Factor Receptor 1 could pave the way for novel NAFLD therapeutics. Thus, it is important to characterize these RTKs for target validation and proof-of-concept through clinical trials.

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.

scholarly journals Nature and Duration of Growth Factor Signaling through Receptor Tyrosine Kinases Regulates HSV-1 Latency in Neurons

2010 ◽  
Vol 8 (4) ◽  
pp. 320-330 ◽  
Author(s):  
Vladimir Camarena ◽  
Mariko Kobayashi ◽  
Ju Youn Kim ◽  
Pamela Roehm ◽  
Rosalia Perez ◽  
...  
Keyword(s):  
Growth Factor ◽  
Tyrosine Kinases ◽  
Receptor Tyrosine Kinases ◽  
Growth Factor Signaling ◽  
Hsv 1
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