A three-state kinetic mechanism for scaffold mediated signal transduction [PDF]
Signaling events in eukaryotic cells are often guided by a scaffolding protein. Scaffold proteins assemble multiple proteins in a spatially localized signaling complex and exert numerous physical effects on signaling pathways. To study these effects, we consider a minimal, three-state kinetic model of scaffold mediated kinase activation.
arxiv +1 more source
Billion-years old proteins show the importance of N-lobe orientation in Imatinib-kinase selectivity [PDF]
The molecular origins of proteins' functions are a combinatorial search problem in the proteins' sequence space, which requires enormous resources to solve. However, evolution has already solved this optimization problem for us, leaving behind suboptimal solutions along the way. Comparing suboptimal proteins along the evolutionary pathway, or ancestors,
arxiv
An unexpected twist to the activation of IKKβ:TAK1 primes IKKβ for activation by autophosphorylation [PDF]
IKKβ {IκB [inhibitor of NF-κB (nuclear factor κB)] kinase β} is required to activate the transcription factor NF-κB, but how IKKβ itself is activated in vivo is still unclear.
Bain+35 more
core +3 more sources
Genomics‐led approach to drug testing in models of undifferentiated pleomorphic sarcoma
GA text Genomic data from undifferentiated pleomorphic sarcoma patients and preclinical models were used to inform a targeted drug screen. Selected compounds were tested in 2D and 3D cultures of UPS cell lines. A combination of trametinib and infigratinib was synergistic in the majority of UPS cell lines tested, which was further confirmed in an ex ...
Piotr J. Manasterski+19 more
wiley +1 more source
A Model of the Roles of Essential Kinases in the Induction and Expression of Late Long-Term Potentiation [PDF]
The induction of late long-term potentiation (L-LTP) involves complex interactions among second messenger cascades. To gain insights into these interactions, a mathematical model was developed for L-LTP induction in the CA1 region of the hippocampus. The differential equation-based model represents actions of protein kinase A (PKA), MAP kinase (MAPK ...
arxiv +1 more source
Mitogen-activated protein kinases mediate Mycobacterium tuberculosis–induced CD44 surface expression in monocytes [PDF]
CD44, an adhesion molecule, has been reported to be a binding site for Mycobacterium tuberculosis (M. tuberculosis) in macrophages and it also mediates mycobacterial phagocytosis, macrophage recruitment and protective immunity against pulmonary ...
Anbalgan, S+2 more
core
Anopheles stephensi p38 MAPK signaling regulates innate immunity and bioenergetics during Plasmodium falciparum infection. [PDF]
BackgroundFruit flies and mammals protect themselves against infection by mounting immune and metabolic responses that must be balanced against the metabolic needs of the pathogens.
Aguirre, Alejandro+13 more
core +1 more source
This study identifies nuclear YB‐1 S102 phosphorylation as a marker associated with KRAS and FBXW7 mutations in colorectal cancer. Mutated KRAS correlates specifically with nuclear, not cytoplasmic, S102 YB‐1. These findings provide the first ex vivo evidence of this link in CRC and suggest future studies should assess the prognostic and therapeutic ...
Konstanze Lettau+9 more
wiley +1 more source
Ancestral resurrection reveals evolutionary mechanisms of kinase plasticity
Protein kinases have evolved diverse specificities to enable cellular information processing. To gain insight into the mechanisms underlying kinase diversification, we studied the CMGC protein kinases using ancestral reconstruction.
Conor J Howard+7 more
doaj +1 more source
Role of protein phosphorylation in cell signaling, disease, and the intervention therapy
Protein phosphorylation is an important post‐transcriptional modification involving an extremely wide range of intracellular signaling transduction pathways, making it an important therapeutic target for disease intervention.
Kun Pang+10 more
doaj +1 more source