Index of papers in PLOS Comp. Biol. that mention
  • kinase
Juan Palacios-Moreno, Lauren Foltz, Ailan Guo, Matthew P. Stokes, Emily D. Kuehn, Lynn George, Michael Comb, Mark L. Grimes
Abstract
In a phosphoproteomic study of neuroblastoma cell lines and cell fractions, including endo-somes and detergent-resistant membranes, 1622 phosphorylated proteins were detected, including more than half ofthe receptortyrosine kinases in the human genome.
Abstract
The analysis indicates that receptor tyrosine kinases are functionally compartmentalized into distinct collaborative groups distinguished by activation and intracellular localization of SRC-family kinases , especially FYN and LYN.
Author Summary
We found that two related proteins (FYN and LYN) act like central hubs in the tyrosine kinase signaling network that change intracellular localization and activity in response to activation of different receptors.
Introduction
Anaplastic lymphoma kinase (ALK), a receptor tyrosine kinase (RTK), is frequently mutated and activated in both familial and spontaneous neuroblastomas, suggesting that this receptor can prevent a key differentiation step in neural crest cells [9—15].
Introduction
Tyrosine kinase signaling networks play a major role in governing cell differentiation, including in neuroblastoma [16].
Introduction
There are 90 tyrosine kinases in the human genome; 58 of these are receptor tyrosine ki-nases [17,18] , many of which have unknown functions.
kinase is mentioned in 44 sentences in this paper.
Topics mentioned in this paper:
Nicolas Guex, Isaac Crespo, Sylvian Bron, Assia Ifticene-Treboux, Eveline Faes-van’t Hull, Solange Kharoubi, Robin Liechti, Patricia Werffeli, Mark Ibberson, Francois Majo, Michäel Nicolas, Julien Laurent, Abhishek Garg, Khalil Zaman, Hans-Anton Lehr, Brian J. Stevenson, Curzio Rüegg, George Coukos, Jean-François Delaloye, Ioannis Xenarios, Marie-Agnès Doucey
Introduction
Recently, monocytes expressing the TIE-2/tek receptor tyrosine kinase (TEM: TIE-2 expressing monocytes) have been identified in peripheral blood and tumors of humans and mouse [34,35].
Introduction
While we have previously reported that TIE-2 and VEGFR kinase
The plasticity of TEM predicted computationally was validated experimentally using TEM differentiated in vitro
The first group of treatments combined TIE-2 tyrosine kinase inhibitor with TGF-B and a ligand of VEGFR-l or TIE-2.
The plasticity of TEM predicted computationally was validated experimentally using TEM differentiated in vitro
Treatments from the second group involved VEGFR-l kinase inhibitor, and the third group of treatments associated TGF-B with TNF-oc and a ligand of TIE-2 or VEGFR-l (Table 4).
The plasticity of TEM predicted computationally was validated experimentally using TEM differentiated in vitro
With currently available tools, VEGFR-l kinase activity is almost impossible to manipulate.
Validation of the predictions in patient TEM- TGF-B/TIE-Z pathways may represent a therapeutic target to inhibit tumor TEM proangiogenic funcfion
Tumor TEM were exposed to TIE-2 kinase inhibitor combined with TGF-B and simultaneously engaged their VEGFR-l using VEGF (alternatively PlGF, Table 4 and Fig.
kinase is mentioned in 13 sentences in this paper.
Topics mentioned in this paper:
Fan Yang, Evangelia Petsalaki, Thomas Rolland, David E. Hill, Marc Vidal, Frederick P. Roth
Abstract
For example, we identified both known and new endometrial cancer hotspots in the tyrosine kinase domain of the FGFR2 protein, one of which is also a hotspot in breast cancer, and found new two hotspots in the Immunoglobulin I-set domain in colon cancer.
Cancer-type-specific positioning of mutations within a given gene
The EGF receptor is a flexible protein with four distinct domains, including extracellular and transmembrane regions, the intracellular kinase domains, and a long flexible tail (Fig.
Cancer-type-specific positioning of mutations within a given gene
Mutations in the extracellular region of EGF receptor have been associated with ligand-independent dimerization in cancers of the central nervous system[46] , and mutations in the intracellular region of EGF receptor are associated with sensitivity to kinase inhibitors[46].
Cancer-type-specific positioning of mutations within a given gene
In lung cancers, mutations were significantly enriched in the tyrosine kinase domain (Pki-nase_Tyr).
Discussion
These five interaction-mediating domain pairs are Bcl-2 and BH4 domains encoded by BCL2, which play important roles in regulating cell death and survival[65]; DEAD and Helicase_C domains encoded by DDX3X, which play important roles in metabolic processes involving RNAs[66]; and PI3Ka and P13K_p85B domains encoded by PIK3CA, which interact with each other to initiate a vast array of signaling events[67]; Furin-like and GF_recep_IV domains encoded by EGFR, which are both extracellular domains of receptor tyrosine protein kinases and which interact with each other to regulate the binding of ligands to the receptor[68]; and finally the DNA binding and P53_tetramer (tetrameriza-tion) domains encoded by TP53.
Discussion
For each cancer type, we found at least one new potential cancer-associated domain instance, for example, the diacylglycerol kinase domain encoded by DGKZ in chondrosarcoma.
Introduction
For example, it was reported that 80% of non-synonymous single-base substitutions observed in genes encoding protein kinases are passenger mutations [24].
Introduction
Similarly, the effects of mutations in different protein kinase sub-domains have been shown to have different functional impacts[28].
Mutational trends of oncoproteins and tumor suppressor proteins
Consistent with this view, we found a single hotspot (p. N549) for FGFR2 in breast cancer in the kinase domain, which had not been reported as a hot-spot for breast cancer.
Mutational trends of oncoproteins and tumor suppressor proteins
Supporting this view, we observed nine evenly-distributed mutated residues in the kinase domain in endometrial cancer, although we also confirm previous observation [54] of the p.N549 hotspot which is more suggestive of an oncoprotein.
Oncogenic mutational hotspots appearing in multiple cancer types
They are V600 in Serine/threonine-protein kinase B-Raf (encoded by BRAF), and R88 and C420 in the phos-phatidylinositol-4,5-bisphosphate 3-kinase encoded by PIK3CA.
kinase is mentioned in 12 sentences in this paper.
Topics mentioned in this paper:
Lorenza A. D’Alessandro, Regina Samaga, Tim Maiwald, Seong-Hwan Rho, Sandra Bonefas, Andreas Raue, Nao Iwamoto, Alexandra Kienast, Katharina Waldow, Rene Meyer, Marcel Schilling, Jens Timmer, Steffen Klamt, Ursula Klingmüller
Abstract
Here, we report a novel hybrid mathematical modeling strategy to systematically unravel hepatocyte growth factor (HGF) stimulated phosphoinosi-tide-3-kinase (PI3K) and mitogen activated protein kinase (MAPK) signaling, which critically contribute to liver regeneration.
Interaction graphs
The applied MEK inhibitor, for example, blocks MEK kinase activity, thus inhibiting the outgoing edges from MEK.
Introduction
Upon binding to its receptor Met, HGF activates the phosphoinositide-(PI)-3-kinase (PI3K) and the mitogen activated protein kinase (MAPK) signaling pathways.
Introduction
In general, activation of PI3K leads to the generation of phosphatidylinositol 3,4,5—triphos-phate (PI3,4,5-P3) that serves as docking site for the serine/threonine protein kinase Akt at the plasma membrane.
Introduction
Activated Raf leads to phosphorylation of a dual specific kinase, the mitogen-activated protein kinase kinase (MEKI and 2), that phosphorylates the extracellular-signal regulated kinase (ERK1 and 2).
kinase is mentioned in 5 sentences in this paper.
Topics mentioned in this paper:
Federica Lombardi, Kalyan Golla, Darren J. Fitzpatrick, Fergal P. Casey, Niamh Moran, Denis C. Shields
Introduction
The activation of GPVI (the only non-GPCR receptor targeted in our study) by Collagen or CRP leads to Lyn and Fyn phosphorylation of the FcR gamma-chain[23] , allowing Syk docking[24] and activation of phospholipase C (PLC)y2 [25] and Phosphoinositide 3 kinase (PISK) [26,27].
Results
We investigated reagents thought to act primarily on siX proteins in pathways of major thera-Epinephrine Receptor (E), P13 Kinase (P), and GPVI Collagen Receptor (C).
Results
There was no inhibitor available for GPVI, and an inhibitor of PI3 kinase was included because of its inhibitory effects on GPVI stimulated activation.
kinase is mentioned in 3 sentences in this paper.
Topics mentioned in this paper:
Ka Wai Lin, Angela Liao, Amina A. Qutub
Discussion
Drugs have been developed to target the IGFIR pathway by suppressing the IGFI to HIFloc pathway using three main types of compounds: IGFIR targeting antibodies, tyrosine kinase inhibitors for kinase domains of IGFIR, and IGFI ligand neutralizing antibodies [24, 77—79].
Discussion
This explains why when U87 and LN229 were targeted using TAE226 (IGFIR tyrosine kinase inhibitor), a larger amount of apoptosis was observed for the LN229 cell line compared to the U87 cells [3].
Insulin signaling interactions in glioblastoma
IGFBP2 was previously shown to interact with integrin alpha 5 [65] , which further signals to Integrin Linked Kinase (ILK).
kinase is mentioned in 3 sentences in this paper.
Topics mentioned in this paper:
Thomas W. Spiesser, Clemens Kühn, Marcus Krantz, Edda Klipp
Introduction
SBF/MBF activity is controlled by the G1 network, which involves the cyclin dependent kinase (CDK) Cdc28, its activating subunits the G1 cyclins Cln1/2/3 and the transcriptional repressor Whi5 (reviewed in [3]).
Introduction
The kinase responsible for mitotic entry Clb2-Cdc28 is inhibited through phosphorylation at the Tyr19 residue by Swe1
The model
Finally, we simplify phase transitions to a threshold for nuclear kinase activity, assuming zero order ultra-sensitivity [60].
kinase is mentioned in 3 sentences in this paper.
Topics mentioned in this paper:
Francisco Martínez-Jiménez, Marc A. Marti-Renom
nAnnoLyze prediction examples
Specifically it is known to inhibit Raf kinases, Receptor-type ty-rosine-protein kinase (FLT3), platelet-derived growth factor (PDGF), Vascular endothelial growth factor receptor 2 & 3 (VEGF2/ 3) and the Mast/stem cell growth factor receptor Kit.
nAnnoLyze prediction examples
However, there are two links not annotated within the predictions, the serine/threonine-protein ki-nase A-Raf (ARAF) and the Cyclin-dependent kinase 10 (CDKIO).
nAnnoLyze prediction examples
Regarding the Cyclin dependent kinases CDK10 and CDK19 proposed binding sites, CDK10 binding site has a high similarity (ProBiS Z-score of 2.09) with the MAPK14 ’s one while the CDK19 binding site is almost identical to that of CDK8 (ProBiS 2.9).
kinase is mentioned in 3 sentences in this paper.
Topics mentioned in this paper: