EPH Receptor Tyrosine Kinases Regulate Epithelial Morphogenesis and Phosphorylate the PAR-3 Scaffold Protein to Modulate Downstream Signaling Networks

2020 ◽  
Author(s):  
Sara L. Banerjee ◽  
Noémie Lavoie ◽  
Kévin Jacquet ◽  
Frédéric Lessard ◽  
Josée N. Lavoie ◽  
...  
Keyword(s):  
Tyrosine Kinases ◽  
Receptor Tyrosine Kinases ◽  
Scaffold Protein ◽  
Epithelial Morphogenesis ◽  
Signaling Networks ◽  
Eph Receptor ◽  
Downstream Signaling

scholarly journals Receptor Tyrosine Kinases Fall into Distinct Classes Based on Their Inferred Signaling Networks

2013 ◽  
Vol 6 (284) ◽  
pp. ra58-ra58 ◽  
Author(s):  
J. P. Wagner ◽  
A. Wolf-Yadlin ◽  
M. Sevecka ◽  
J. K. Grenier ◽  
D. E. Root ◽  
...  
Keyword(s):  
Tyrosine Kinases ◽  
Receptor Tyrosine Kinases ◽  
Signaling Networks

scholarly journals In vitro guidance of retinal ganglion cell axons by RAGS, a 25 kDa tectal protein related to ligands for Eph receptor tyrosine kinases

Cell ◽  
1995 ◽  
Vol 82 (3) ◽  
pp. 359-370 ◽  
Author(s):  
Uwe Drescher ◽  
Claus Kremoser ◽  
Claudia Handwerker ◽  
Jürgen Löschinger ◽  
Masaharu Noda ◽  
...  
Keyword(s):  
Ganglion Cell ◽  
Retinal Ganglion Cell ◽  
Tyrosine Kinases ◽  
Receptor Tyrosine Kinases ◽  
Retinal Ganglion ◽  
Eph Receptor

scholarly journals A new ephrin-A1 isoform (ephrin-A1b) with altered receptor binding properties abrogates the cleavage of ephrin-A1a

2004 ◽  
Vol 379 (1) ◽  
pp. 39-46 ◽  
Author(s):  
Eivind F. FINNE ◽  
Else MUNTHE ◽  
Hans-Christian AASHEIM
Keyword(s):  
Tyrosine Kinases ◽  
Receptor Tyrosine Kinases ◽  
Transcript Level ◽  
Binding Properties ◽  
Eph Receptor ◽  
Cleavage Process ◽  
293 Cells ◽  
Significant Expression ◽  
Isoform B ◽  
Epha Receptor

Ephrins are ligands for the Eph receptor tyrosine kinases, which play important roles in patterning nervous and vascular systems. Ephrin-A1 is a glycosylphosphatidylinositol-anchored ligand that binds to the EphA receptor tyrosine kinases. In the present study, we have identified a new ephrin-A1 isoform, denoted ephrin-A1b (ephrin-A1 isoform b). Compared with the originally described ephrin-A1 sequence, ephrin-A1a [Holzman, Marks and Dixit (1990) Mol. Cell. Biol. 10, 5830–5838], ephrin-A1b lacks a segment of 22 amino acids (residues 131–152). At the transcript level, exon 3 is spliced out in the transcript encoding ephrin-A1b. Transfection of HEK-293T cells (human embryonic kidney 293 cells) with an ephrin-A1b-expressing plasmid resulted in a significant expression of the protein on the cell surface. However, soluble EphA2 receptor (EphA2-Fc) bound weakly to ephrin-A1b-expressing transfectants, but bound strongly to ephrin-A1a-expressing transfectants. Ephrins have been shown to undergo regulated cleavage after interaction with their receptors. This process is inhibited by co-expression of ephrin-A1a and ephrin-A1b, indicating that ephrin-A1b influences the cleavage process. Taken together, these findings indicate that this newly described isoform may regulate the function of its ephrin-A1a counterpart.

scholarly journals Receptor Tyrosine Kinases in Kidney Development

2011 ◽  
Vol 2011 ◽  
pp. 1-10 ◽  
Author(s):  
Renfang Song ◽  
Samir S. El-Dahr ◽  
Ihor V. Yosypiv
Keyword(s):  
Tyrosine Kinases ◽  
Molecular Mechanisms ◽  
Kidney Development ◽  
Receptor Tyrosine Kinases ◽  
Adaptor Proteins ◽  
Downstream Signaling ◽  
Arterial Blood ◽  
Intracellular Signal ◽  
Human Birth

The kidney plays a fundamental role in the regulation of arterial blood pressure and fluid/electrolyte homeostasis. As congenital anomalies of the kidney and urinary tract (CAKUT) constitute one of the most common human birth defects, improved understanding of the cellular and molecular mechanisms that lead to CAKUT is critical. Accumulating evidence indicates that aberrant signaling via receptor tyrosine kinases (RTKs) is causally linked to CAKUT. Upon activation by their ligands, RTKs dimerize, undergo autophosphorylation on specific tyrosine residues, and interact with adaptor proteins to activate intracellular signal transduction pathways that regulate diverse cell behaviours such as cell proliferation, survival, and movement. Here, we review the current understanding of role of RTKs and their downstream signaling pathways in the pathogenesis of CAKUT.

scholarly journals Receptor Tyrosine Kinases and Their Signaling Pathways as Therapeutic Targets of Curcumin in Cancer

2021 ◽  
Vol 12 ◽  
Author(s):  
Sareshma Sudhesh Dev ◽  
Syafiq Asnawi Zainal Abidin ◽  
Reyhaneh Farghadani ◽  
Iekhsan Othman ◽  
Rakesh Naidu
Keyword(s):  
Signaling Pathways ◽  
Cancer Progression ◽  
Tyrosine Kinases ◽  
Receptor Tyrosine Kinases ◽  
Surface Proteins ◽  
Downstream Signaling ◽  
Anti Cancer ◽  
Rtk Inhibitors

Receptor tyrosine kinases (RTKs) are transmembrane cell-surface proteins that act as signal transducers. They regulate essential cellular processes like proliferation, apoptosis, differentiation and metabolism. RTK alteration occurs in a broad spectrum of cancers, emphasising its crucial role in cancer progression and as a suitable therapeutic target. The use of small molecule RTK inhibitors however, has been crippled by the emergence of resistance, highlighting the need for a pleiotropic anti-cancer agent that can replace or be used in combination with existing pharmacological agents to enhance treatment efficacy. Curcumin is an attractive therapeutic agent mainly due to its potent anti-cancer effects, extensive range of targets and minimal toxicity. Out of the numerous documented targets of curcumin, RTKs appear to be one of the main nodes of curcumin-mediated inhibition. Many studies have found that curcumin influences RTK activation and their downstream signaling pathways resulting in increased apoptosis, decreased proliferation and decreased migration in cancer both in vitro and in vivo. This review focused on how curcumin exhibits anti-cancer effects through inhibition of RTKs and downstream signaling pathways like the MAPK, PI3K/Akt, JAK/STAT, and NF-κB pathways. Combination studies of curcumin and RTK inhibitors were also analysed with emphasis on their common molecular targets.

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 SRC Kinase in Glioblastoma: News from an Old Acquaintance

Cancers ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1558 ◽  
Author(s):  
Claudia Cirotti ◽  
Claudia Contadini ◽  
Daniela Barilà
Keyword(s):  
Receptor Tyrosine Kinase ◽  
Tyrosine Kinases ◽  
Receptor Tyrosine Kinases ◽  
Metabolic Reprogramming ◽  
Constitutive Activity ◽  
Therapeutic Approaches ◽  
Resistance To Therapy ◽  
Downstream Signaling ◽  
Wide Range ◽  
Therapy Effectiveness

Glioblastoma multiforme (GBM) is one of the most recalcitrant brain tumors characterized by a tumor microenvironment (TME) that strongly supports GBM growth, aggressiveness, invasiveness, and resistance to therapy. Importantly, a common feature of GBM is the aberrant activation of receptor tyrosine kinases (RTKs) and of their downstream signaling cascade, including the non-receptor tyrosine kinase SRC. SRC is a central downstream intermediate of many RTKs, which triggers the phosphorylation of many substrates, therefore, promoting the regulation of a wide range of different pathways involved in cell survival, adhesion, proliferation, motility, and angiogenesis. In addition to the aforementioned pathways, SRC constitutive activity promotes and sustains inflammation and metabolic reprogramming concurring with TME development, therefore, actively sustaining tumor growth. Here, we aim to provide an updated picture of the molecular pathways that link SRC to these events in GBM. In addition, SRC targeting strategies are discussed in order to highlight strengths and weaknesses of SRC inhibitors in GBM management, focusing our attention on their potentialities in combination with conventional therapeutic approaches (i.e., temozolomide) to ameliorate therapy effectiveness.

Sign in / Sign up

Export Citation Format

Share Document