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Kinases are enzymes that catalyze the addition of a phosphate group (PO43−) to substrates, usually proteins. The phosphate generally comes from adenosine triphosphate (ATP). Kinases and phosphatases, which remove phosphate groups, are involved in nearly all signal transduction processes, often with cascades of phosphorylation events.
A new study reveals that the RAF isoform ARAF uniquely forms solid-like granules at the cell membrane that have a key role in regulating RAS activation levels and contribute to drug resistance.
The apical–basal polarity of epithelial cells depends on mutual antagonism between the apical aPKC and lateral LGL proteins. Until now, it has been unclear how LGL can be both a substrate and inhibitor of aPKC. Now, a cryo-electron microscopy (cryo-EM) structure of a stalled PAR6–aPKC–LGL complex addresses this conundrum.
Here, the authors develop hydrocarbon-stapled paxillin-mimetic peptides that act as selective and potent focal adhesion kinase (FAK) scaffold inhibitors to displace FAK from focal adhesions. Treatment shows reduced cancer cell survival in vitro and reduced tumor burden in vivo.
The PEAK family of pseudokinases is known to play oncogenic roles in poor-prognosis triple negative breast cancer (TNBC). Here this group identifies the role of calcium/calmodulin-dependent protein kinase 2 (CAMK2) in targeting downstream of PEAK1 thereby utilizing RA306 (CAMK2 inhibitor) to effectively attenuate TNBC xenograft growth and block metastasis as well.
This study identifies FOXN3 as a suppressor of pulmonary fibrosis by inhibiting Smad signaling. FOXN3 facilitates Smad4 ubiquitination, disrupting the Smad complex’s association with target elements and abolishing its transcriptional activity.
Haspin phosphorylates histone H3 threonine 3 (H3T3) to ensure proper progression through mitosis. Here the authors describe how Haspin engages a nucleosomal DNA supergroove, using electrostatic interactions, thereby promoting H3T3 phosphorylation.
Kinases are attractive drug targets, but the design of highly selective kinase inhibitors remains challenging. Here, the authors report photoaffinity probes based on the imidazopyrazine scaffold, which is found in several kinase inhibitors and drugs or drug candidates, and use proteome selectivity profiling to show the varying off-target profiles of different probes.
A new study reveals that the RAF isoform ARAF uniquely forms solid-like granules at the cell membrane that have a key role in regulating RAS activation levels and contribute to drug resistance.
The apical–basal polarity of epithelial cells depends on mutual antagonism between the apical aPKC and lateral LGL proteins. Until now, it has been unclear how LGL can be both a substrate and inhibitor of aPKC. Now, a cryo-electron microscopy (cryo-EM) structure of a stalled PAR6–aPKC–LGL complex addresses this conundrum.
Ferroptosis, a cell death mechanism induced by lipid peroxidation, is pivotal in tumor suppression. A recent study shows that tumor repopulating cells evade ferroptosis and develop resistance to therapy via subverting a lipid metabolism enzyme.
Understanding the role of pyrophosphorylation requires specific analytical strategies to discriminate it from protein phosphorylation. A custom workflow reveals that nucleolar protein pyrophosphorylation in human cells regulates the transcription of ribosomal DNA.
Reprogramming intercellular mechanotransduction and signaling pathways is still challenging. A recent advance uses a plug-and-play DNA nanodevice to allow non-mechanosensitive receptor tyrosine kinase (RTK) to transmit force-induced cellular signals.
