Complexity of Receptor Tyrosine Kinase Signal Processing
Reads0
Chats0
TLDR
This work discusses how RTK network regulatory structures, which involve the immediate posttranslational and delayed transcriptional controls by multiple feed forward and feedback loops together with pathway cross talk, adapt cells to the combinatorial variety of external cues and conditions.Abstract:
Our knowledge of molecular mechanisms of receptor tyrosine kinase (RTK) signaling advances with ever-increasing pace. Yet our understanding of how the spatiotemporal dynamics of RTK signaling control specific cellular outcomes has lagged behind. Systems-centered experimental and computational approaches can help reveal how overlapping networks of signal transducers downstream of RTKs orchestrate specific cell-fate decisions. We discuss how RTK network regulatory structures, which involve the immediate posttranslational and delayed transcriptional controls by multiple feed forward and feedback loops together with pathway cross talk, adapt cells to the combinatorial variety of external cues and conditions. This intricate network circuitry endows cells with emerging capabilities for RTK signal processing and decoding. We illustrate how mathematical modeling facilitates our understanding of RTK network behaviors by unraveling specific systems properties, including bistability, oscillations, excitable responses, and generation of intricate landscapes of signaling activities.read more
Citations
More filters
Journal ArticleDOI
The dynamic control of signal transduction networks in cancer cells.
TL;DR: This Review discusses recent concepts concerning how the rich signalling dynamics afforded by these networks are regulated and how they impinge on cancer cell proliferation, survival, invasiveness and drug resistance.
Journal ArticleDOI
Advances in developing novel therapeutic strategies for Alzheimer’s disease
TL;DR: Current strategies and new trends of AD drug development are summarized, including pre-clinical and clinical trials that target different aspects of disease (mechanism-based versus non-mechanisms based, e.g. symptomatic treatments, lifestyle modifications and risk factor management).
Journal ArticleDOI
Proteolytic cleavage, trafficking, and functions of nuclear receptor tyrosine kinases
TL;DR: The proteolytic processing, intracellular trafficking and nuclear functions of RTKs are summarized, and how they promote cancer progression, and their clinical implications are discussed.
Journal ArticleDOI
Amplification of Wild-type KRAS Imparts Resistance to Crizotinib in MET Exon 14 Mutant Non-Small Cell Lung Cancer.
Magda Bahcall,Mark M. Awad,Lynette M. Sholl,Frederick H. Wilson,Man Xu,Stephen Wang,Sangeetha Palakurthi,Jihyun Choi,Elena Ivanova,Giulia Costanza Leonardi,Bryan C. Ulrich,Cloud P. Paweletz,Paul Kirschmeier,Masayuki Watanabe,Hideo Baba,Mizuki Nishino,Rebecca J. Nagy,Richard B. Lanman,Marzia Capelletti,Emily S. Chambers,Amanda J. Redig,Amanda J. Redig,Paul A. VanderLaan,Daniel B. Costa,Yu Imamura,Yu Imamura,Pasi A. Jänne,Pasi A. Jänne +27 more
TL;DR: The mechanism of crizotinib resistance mediated by KRAS amplification in METex14-mutant NSCLC is characterized and the superior efficacy of the dual MET/PI3K inhibition as a therapeutic strategy addressing this resistance mechanism is demonstrated.
Journal ArticleDOI
Cross-Talk between Fibroblast Growth Factor Receptors and Other Cell Surface Proteins
Marta Latko,Aleksandra Czyrek,Natalia Porębska,Marika Kucińska,Jacek Otlewski,Malgorzata Zakrzewska,Łukasz Opaliński +6 more
TL;DR: Current stage of knowledge about the regulation ofFGFRs by the plasma membrane-embedded partner proteins is summarized and the importance of FGFRs-containing membrane complexes in pathological conditions, including cancer, is highlighted.
References
More filters
Journal ArticleDOI
Cell signaling by receptor-tyrosine kinases
TL;DR: Understanding of the complex signaling networks downstream from RTKs and how alterations in these networks are translated into cellular responses provides an important context for therapeutically countering the effects of pathogenic RTK mutations in cancer and other diseases.
Journal ArticleDOI
Network Motifs: Simple Building Blocks of Complex Networks
TL;DR: Network motifs, patterns of interconnections occurring in complex networks at numbers that are significantly higher than those in randomized networks, are defined and may define universal classes of networks.
Journal ArticleDOI
Signaling--2000 and beyond.
TL;DR: The important findings in the history of signal transduction are adequately covered in many reviews, and I have therefore cited reviews that discuss the seminal papers.
Journal ArticleDOI
Stochastic mechanisms in gene expression
Harley H. McAdams,Adam P. Arkin +1 more
TL;DR: This work has analyzed the chemical reactions controlling transcript initiation and translation termination in a single such "genetically coupled" link as a precursor to modeling networks constructed from many such links.
Journal ArticleDOI
Structure and function of the feed-forward loop network motif
S. Mangan,Uri Alon +1 more
TL;DR: This study defines the function of one of the most significant recurring circuit elements in transcription networks, the feed-forward loop (FFL), which is a three-gene pattern composed of two input transcription factors, both jointly regulating a target gene.
Related Papers (5)
Specificity of receptor tyrosine kinase signaling: Transient versus sustained extracellular signal-regulated kinase activation
Feedback regulation of EGFR signalling: decision making by early and delayed loops.
Roi Avraham,Yosef Yarden +1 more