Ask about this productRelated genes to: Aak1 Blocking Peptide
- Gene:
- AAK1 NIH gene
- Name:
- AP2 associated kinase 1
- Previous symbol:
- -
- Synonyms:
- KIAA1048, DKFZp686K16132
- Chromosome:
- 2p13.3
- Locus Type:
- gene with protein product
- Date approved:
- 2003-07-21
- Date modifiied:
- 2015-08-24
Related products to: Aak1 Blocking Peptide
Related articles to: Aak1 Blocking Peptide
- AAK1 and BMP2K are serine/threonine kinases traditionally known for phosphorylating AP2 during clathrin-mediated endocytosis (CME), but their broader roles remained incompletely defined. Here, using motif-guided in silico, biochemical, and phosphoproteomic screens, we identify PDLIM5 and Talin1 as direct AAK1/BMP2K substrates. Despite high kinase-domain similarity, only AAK1 promotes cell migration and potentiates focal adhesion (FA) turnover. Live-cell imaging shows that AAK1 recruitment to FAs peaks as disassembly begins. The conserved AAK1 C-terminal PDZ-binding motif mediates direct, low-affinity binding to PDLIM5, providing a plausible mechanism for localized substrate access. Dynamic analyses of phospho-mimetic and phospho-null mutants support a model in which AAK1-dependent phosphorylation promotes timely release of PDLIM5 and Talin1 during FA disassembly. These findings reveal a kinase-driven contribution to FA turnover distinct from protease- and phosphatase-based mechanisms and suggest that functional divergence between AAK1 and BMP2K may provide a strategy to modulate cell migration with reduced impact on CME. - Source: PubMed
Publication date: 2026/05/04
Krocianova DanielaDagg Alexander DClayton Rory APotesil DavidFedorova VeronikaHarmanec AdamBenova ViktoriaBosakova VeronikaKaufman Jonathan G GMartinkova PetraAlblova MiroslavaKelly Bernard THanakova KaterinaRoudnicky PavelSpielman Stephanie JFric JanSroubek FilipHouser JosefWrobel Antoni GBoura EvzenOwen David JZdrahal ZbynekKadlecova Zuzana - Painful diabetic peripheral neuropathy (PDPN) remains a serious complication of diabetes mellitus (DM). Recent clinical trials have demonstrated promising outcomes for pilavapadin (LX9211), an orally administered selective, potent inhibitor of adapter protein-2-associated kinase 1 (AAK1) and vixotrigine, a broad spectrum voltage-gated sodium channels (Navs) inhibitor. Their beneficial role was reflected in improved average daily pain (ADP) score and Patient Global Impression of Change (PGIC). Gamma-aminobutyric acid (GABA) receptor agonism has yielded favourable outcomes in preliminary studies. Experimental studies have further expanded the spectrum of potential agents, therapeutic targets and mechanisms in PDPN. Some of potential therapeutic approaches include chemokine suppression (CCR2/CCR5 or CXCR1/2 inhibition) and transient receptor potential vanilloid 1 (TRPV1) pathway suppression. Impaired mitochondrial function in PDPN is now being discussed and the inhibition of poly (adenosine diphosphate [ADP]-ribose) polymerase 1(PARP1), a mitochondrial enzyme responsible for deoxyribonucleic acid (DNA) repair is emerging. Local treatments have also been examined in animal models, such as resiniferatoxin. Limited evidence exists regarding the therapeutic potential of antidiabetic agents, glucagon-like peptide-1 receptor agonists (GLP-1RAs), being most widely studied in experimental settings. Future large clinical trials are now required to confirm the efficacy of novel promising agents and to delineate further potential favourable effects of antidiabetic agents in clinical settings. - Source: PubMed
Publication date: 2026/03/31
Panou TheodorosPapanas NikolaosKempler Peter - Porcine reproductive and respiratory syndrome virus (PRRSV) is a major pathogen that poses a considerable threat to the global swine industry, particularly with emerging variants that complicate control efforts. However, the host factors involved in PRRSV entry are not well understood. In the present study, we identified members of the numb-associated kinase (NAK) family, specifically adaptor-associated kinase 1 (AAK1), G-associated kinase (GAK), and BMP-2-inducible kinase (BMP2K), as essential regulators of PRRSV entry utilizing both genetic and pharmacological approaches. Mechanistically, NAKs facilitate PRRSV entry by phosphorylating the adaptor protein complex 2 subunit mu-1 (AP2M1) at threonine 156, enhancing AP2M1 activation and thereby promoting its interaction with the YxxØ motif in PRRSV glycoprotein (GP) 5 and the receptor cluster of differentiation 163 (CD163). This interaction is critical for efficient trafficking of the virions to early endosomes (EEs). Disruption of AP2M1 phosphorylation or blockade of the AP2M1-YxxØ interaction significantly impaired PRRSV internalization, indicating the potential for targeting this pathway to inhibit infection. Notably, inhibition of the NAKs-AP2M1 axis effectively reduced infection across multiple PRRSV strains, highlighting its capacity as a broad-spectrum antiviral target. Collectively, our findings provide novel insights into PRRSV entry mechanisms and offer a promising therapeutic strategy to control emerging variants of this economically significant disease. - Source: PubMed
Publication date: 2026/04/13
Zhang LongxiangLi RuiYou LingqiaoJiang YanWang XinrongZhu JunhaiYan NanWang Yue - Sheep production contributes to a secure and diverse food and fibre supply in the United States, with growing ethnic diversity strengthening demand. Katahdin is a composite hair-type sheep breed developed in the United States that has become the most popular breed in many regions of the country and the first one to have genomic selection implemented in its breeding program. Therefore, the main objectives of this study were to estimate variance components of reproductive traits, including number of lambs born (NLB), number of lambs weaned (NLW), age at first lambing (AFL), and interval from first to second lambing (LI), in Katahdin sheep using the AIREML method and the single-step Genomic Best Linear Unbiased Prediction (ssGBLUP) approach, and to identify genomic regions and candidate genes associated with these traits. The datasets used consisted of 127,536 animals in the pedigree, phenotypic records of 56,128 parities from 24,067 ewes, and genomic data from 10,032 animals with 30,308 single-nucleotide polymorphisms (SNP) after quality control. Analyses were performed using the BLUPF90 family of programs. We observed low heritability estimates for all studied traits (0.09 ± 0.00 for NLB, 0.08 ± 0.00 for NLW, 0.09 ± 0.01 for AFL, and 0.08 ± 0.01 for LI). The genetic correlations between the traits ranged from 0.17 ± 0.02 (AFL and LI) to 0.79 ± 0.02 (NLB and NLW). All traits were found to be highly polygenic with all 14 significant SNP on eight (OAR) chromosomes (3, 6, 7, 8, 9, 12, 13, and 15) having small effects on the total variability on the traits. These SNP were located near or within 18 candidate genes: four genes associated with NLB (AAK1, GFPT1, SLC23A2, and GDAP1), four with NLW (ARHGAP18, TTLL2, UNC93A, and GPR31), six with AFL (NAP1L5, FAM13A, HS3ST1, CCDC181, NME7, and BLZF1), and four with LI (TAF4, CDH4, CADM1, and SEL1L). These candidate genes have been previously associated with fertility, embryonic development, growth, disease resistance, and climatic adaptation traits. Our findings indicate that fertility and reproduction traits in Katahdin sheep can be improved through direct genetic selection. Genetic improvement for these traits will benefit from genomic selection as more accurate estimates of breeding values for selection candidates can be obtained at a younger age. Although the studied traits are influenced by a complex interplay of genetic and environmental factors, the candidate genes identified enabled a better understanding of the biological mechanisms underlying reproductive performance in Katahdin sheep. - Source: PubMed
Publication date: 2026/03/30
Ospina Alejandra ToroLewis Ronald MFreking Bradley ABurke Joan MMurphy Thomas WWilson Carrie SBrito Luiz F - The interplay between genetic factors and COVID-19 susceptibility and severity underscores the critical roles of genetic variations in the responses to the virus. Specifically, genetic variations in genes such as AAK1 and ADAM17 may influence the molecular pathways that determine how the virus enters cells and how the immune system responds, thereby affecting disease outcomes. Identifying these potential genetic variants clarifies individual responses to infectious diseases and helps aid in developing effective targeted therapeutic strategies. - Source: PubMed
Publication date: 2026/02/27
Bouzid AmalElemam Noha MAlsafar HabibaVenkatachalam ThenmozhiEldoahji LeenHalabi NourSaleh Mohamed ATalaat Iman MTaneera JalalSulaiman NabilMaghazachi Azzam AHamid QutaybaHamoudi RifatSaber-Ayad Maha