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Receptor Kinase

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lightbulbAbout this topic
Receptor kinases are a class of membrane-bound proteins that function as enzymes, phosphorylating specific tyrosine residues on themselves or other proteins in response to ligand binding. This phosphorylation initiates intracellular signaling cascades that regulate various cellular processes, including growth, differentiation, and metabolism.
lightbulbAbout this topic
Receptor kinases are a class of membrane-bound proteins that function as enzymes, phosphorylating specific tyrosine residues on themselves or other proteins in response to ligand binding. This phosphorylation initiates intracellular signaling cascades that regulate various cellular processes, including growth, differentiation, and metabolism.

Key research themes

1. How do conformational states and binding site features of receptor kinase domains influence selective inhibition and drug resistance?

This research theme focuses on the structural dynamics of receptor kinase activation states—particularly the active (DFG-in) and inactive (DFG-out) conformations—and how these conformations define the binding modes and selectivity profiles of small-molecule kinase inhibitors. Understanding these molecular features is crucial for rational drug design that overcomes cross-reactivity and acquired resistance mechanisms in cancer therapies.

Key finding: This paper delineates the molecular basis of small-molecule kinase inhibition, distinguishing type I inhibitors that bind the ATP site in the active (DFG-in) conformation from type II inhibitors that target the ATP site plus... Read more
Key finding: Using in silico docking studies across 19 kinases, this work showed how binding pocket structural variations, including mutations, influence drug affinity and selectivity profiles. It emphasized that subtle conformational... Read more
Key finding: This comprehensive review establishes protein kinase conformational switching as a core regulatory mechanism, describing the structural hallmarks of active versus inactive states, including the critical role of the regulatory... Read more
Key finding: This study elaborates on the enzyme kinetics, structural biology, and regulatory mechanisms of protein kinases, highlighting the conserved bilobal architecture that creates the ATP-binding pocket crucial for inhibitor... Read more

2. What are the mechanisms and specificity determinants of receptor tyrosine kinase activation and substrate phosphorylation, including autophosphorylation and downstream signaling?

This theme examines the molecular basis of receptor tyrosine kinase (RTK) activation, including autophosphorylation in activation loops and C-terminal tails, and how these phosphorylation events modulate kinase catalytic activity and substrate specificity. It also explores kinase-substrate recognition motifs, docking interactions, and phosphorylation site preferences that determine specificity in complex signaling networks. These mechanisms underpin the regulation of cellular functions such as proliferation and survival, with implications for targeted therapeutics.

by B. Murray and 
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Key finding: Through enzymatic analyses, this paper reveals that autophosphorylation of the Tie2 receptor tyrosine kinase enhances its kinase catalytic activity via phosphorylation of the activation loop, inducing conformational changes... Read more
Key finding: This work defines consensus docking (D-domain) and phosphorylation motifs within MAPK substrates, identifying clusters of basic residues and hydrophobic motifs as key determinants for kinase-substrate specificity. The study... Read more
Key finding: Using synthetic peptides, this paper establishes that Protein Kinase C (PKC) and cAMP-dependent Protein Kinase (PKA) differ in substrate recognition despite shared requirements for proximal basic residues. PKC preferentially... Read more
Key finding: This study identifies specific receptor proteins (RACKs) as intracellular targets mediating Protein Kinase C (PKC) translocation and function. It characterizes a common PKC-binding sequence and demonstrates that peptides... Read more

3. How can large-scale proteomic and interactome mapping advance understanding of receptor tyrosine kinase regulation and kinase-phosphatase networks?

Focused on systems-level studies, this theme integrates mass spectrometry-based phosphoproteomics, protein-protein interaction mapping, and inhibitor profiling to construct comprehensive regulatory networks involving receptor tyrosine kinases (RTKs), their substrates, and interacting phosphatases. These approaches enable identification of kinase-substrate relationships, kinase co-regulation patterns, and phosphatase-mediated control mechanisms, providing crucial insights into signaling complexities, resistance mechanisms, and potential combinatorial therapeutic targets.

Key finding: By compiling nearly 3 million phosphopeptide measurements across 399 conditions, this study infers activity profiles for 215 human kinases, revealing global kinase co-regulation patterns and defining 'generalist' kinases... Read more
Key finding: Utilizing membrane yeast two-hybrid and mammalian membrane two-hybrid assays, this work maps an extensive RTK-phosphatase protein-protein interaction network, uncovering numerous novel interactions. It reveals distinct... Read more
Key finding: Introducing the KiPIK method, this study uses comprehensive kinase inhibitor activity profiles to fingerprint and identify upstream kinases responsible for phosphorylation at specific sites in cell extracts. Validation on... Read more
Key finding: This paper employs mass spectrometry combined with targeted pharmacological inhibition to elucidate reciprocal activation and crosstalk among RTKs (e.g., MET, EGFR, IGF1R, PDGFR) in cancer cell lines. The study quantitatively... Read more

All papers in Receptor Kinase

SummaryBecause they are tethered in space, plants have to make the most of their local growth environment. In order to grow in an ever‐changing environment, plants constantly remodel their shapes. This adaptive attribute requires the... more
Growth factor signaling results in dramatic phenotypic changes in cells, which require commensurate alterations in cellular metabolism. Mutations in SLC2A10/GLUT10, a member of the facilitative glucose transporter family, are associated... more
Receptor kinases play important roles in plant growth and development, but only few of them have been functionally characterized in depth. Over the past decade CRINKLY 4 (CR4)-related research has peaked as a result of a newly discovered... more
Pathogen perception by plants is mediated by plasma membrane-localized immune receptors that have varied extracellular domains. Lectin receptor kinases (LecRKs) are among these receptors and are subdivided into 3 classes, C-type LecRKs... more
High input costs and environmental pressures to reduce nitrogen use in agriculture have increased the competitive advantage of legume crops. The symbiotic relationship that legumes form with nitrogen-fixing soil bacteria in root nodules... more
To ensure fertility, complex somatic and germinal cell proliferation and differentiation programs must be executed in flowers. Loss-of-function of the maize multiple archesporial cells 1 (mac1) gene increases the meiotically competent... more
Nodulation factor (NF) signal transduction in the legume-rhizobium symbiosis involves calcium oscillations that are instrumental in eliciting nodulation. To date, Ca2+ spiking has been studied exclusively in the intracellular bacterial... more
CLE peptides are potentially involved in nodule organ development and in the autoregulation of nodulation (AON), a systemic process that restricts nodule number. A genome-wide survey of CLE peptide genes in the soybean glycine max genome... more
The wall-associated kinases (WAKs) are a family of transmembrane proteins involved in pathogen responses and cell elongation in Arabidopsis. They belong to the major receptor-like kinase (RLK) family in plants. Given their architecture... more
Short-term muscle denervation is a reproducible model of tissue-specific insulin resistance. To investigate the molecular basis of insulin resistance in denervated muscle, the downstream signaling molecules of the insulin-signaling... more
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