ArticlePLoS biology2019
Comprehensive profiling of the STE20 kinase family defines features essential for selective substrate targeting and signaling output.
Article in PLoS biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 54 citations in OpenAlex.
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- Thousand-And-One Kinase 3 in Pancreatic Ductal Adenocarcinoma Stemness, Microenvironment and Therapy Resistance.International journal of molecular sciences · 2026Review
- The LOK C-terminus is an IBAR-like domain that facilitates membrane binding and ezrin colocalization.Biophysical journal · 2026Article
- The fast-evolving FIKK kinase family of Plasmodium falciparum can be inhibited by a single compound.Nature microbiology · 2025Article
- Expanding the phenotype and genotype spectrum of TAOK1 neurodevelopmental disorder and delineating TAOK2 neurodevelopmental disorder.Genetics in medicine : official journal of the American College of Medical Genetics · 2025Article
- Multi-Omics Analysis Revealed That TAOK1 Can Be Used as a Prognostic Marker and Target in a Variety of Tumors, Especially in Cervical Cancer.OncoTargets and therapy · 2025Article
- Genetic Encoding of Phosphorylated Amino Acids into Proteins.Chemical reviews · 2024Review
- The role of TAOK3 in cancer progression and development as a prognostic marker: A pan-cancer analysis study.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2024Article
- Pleiotropic functions of TAO kinases and their dysregulation in neurological disorders.Science signaling · 2024Review
- Epinephrine inhibits PI3Kα via the Hippo kinases.Cell reports · 2023Article
- TAOK3 limits age-associated inflammation by negatively modulating macrophage differentiation and their production of TNFα.Immunity & ageing : I & A · 2023Article
- Proteome-wide screening for mitogen-activated protein kinase docking motifs and interactors.Science signaling · 2023Article
- Neurodevelopmental disorder-associated mutations in TAOK1 reveal its function as a plasma membrane remodeling kinase.Science signaling · 2023Article
- Rho family GTPase signaling through type II p21-activated kinases.Cellular and molecular life sciences : CMLS · 2022Review
- De Novo Discovery of Thiopeptide Pseudo-natural Products Acting as Potent and Selective TNIK Kinase Inhibitors.Journal of the American Chemical Society · 2022Article
- Engineered kinases as a tool for phosphorylation of selected targets in vivo.The Journal of cell biology · 2022Article
- A Stk4-Foxp3-NF-κB p65 transcriptional complex promotes TScience immunology · 2022Article
- Hippo pathway monomerizes STAT3 to regulate prostate cancer growth.Cancer science · 2022Article
- Paternal De Novo Variant ofFrontiers in genetics · 2022Article
- Identification of a dual TAOK1 and MAP4K5 inhibitor using a structure-based virtual screening approach.Journal of enzyme inhibition and medicinal chemistry · 2021Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
Abstract
Specificity within protein kinase signaling cascades is determined by direct and indirect interactions between kinases and their substrates. While the impact of localization and recruitment on kinase-substrate targeting can be readily assessed, evaluating the relative importance of direct phosphorylation site interactions remains challenging. In this study, we examine the STE20 family of protein serine-threonine kinases to investigate basic mechanisms of substrate targeting. We used peptide arrays to define the phosphorylation site specificity for the majority of STE20 kinases and categorized them into four distinct groups. Using structure-guided mutagenesis, we identified key specificity-determining residues within the kinase catalytic cleft, including an unappreciated role for the kinase β3-αC loop region in controlling specificity. Exchanging key residues between the STE20 kinases p21-activated kinase 4 (PAK4) and Mammalian sterile 20 kinase 4 (MST4) largely interconverted their phosphorylation site preferences. In cells, a reprogrammed PAK4 mutant, engineered to recognize MST substrates, failed to phosphorylate PAK4 substrates or to mediate remodeling of the actin cytoskeleton. In contrast, this mutant could rescue signaling through the Hippo pathway in cells lacking multiple MST kinases. These observations formally demonstrate the importance of catalytic site specificity for directing protein kinase signal transduction pathways. Our findings further suggest that phosphorylation site specificity is both necessary and sufficient to mediate distinct signaling outputs of STE20 kinases and imply broad applicability to other kinase signaling systems.
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