ArticleBiochimica et biophysica acta2013
HIPK2 catalytic activity and subcellular localization are regulated by activation-loop Y354 autophosphorylation.
Article in Biochimica et biophysica acta, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 48 citations in OpenAlex.
- Critical role of the CMGC insert sequence for tyrosine autophosphorylation in the protein kinase DYRK1B.Scientific reports · 2025Article
- HIPK2 in Colon Cancer: A Potential Biomarker for Tumor Progression and Response to Therapies.International journal of molecular sciences · 2024Review
- Cumulative Dose from Recurrent CT Scans: Exploring the DNA Damage Response in Human Non-Transformed Cells.International journal of molecular sciences · 2024Article
- Functions of SRPK, CLK and DYRK kinases in stem cells, development, and human developmental disorders.FEBS letters · 2023Review
- HIPK2 in the physiology of nervous system and its implications in neurological disorders.Biochimica et biophysica acta. Molecular cell research · 2023Review
- Differential maturation and chaperone dependence of the paralogous protein kinases DYRK1A and DYRK1B.Scientific reports · 2022Article
- HIPK2 phosphorylates HDAC3 for NF-κB acetylation to ameliorate colitis-associated colorectal carcinoma and sepsis.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- An Alternative Splice Variant of HIPK2 with Intron Retention Contributes to Cytokinesis.Cells · 2020Article
- Chromatin Targeting of HIPK2 Leads to Acetylation-Dependent Chromatin Decondensation.Frontiers in cell and developmental biology · 2020Article
- Extrachromosomal Histone H2B Contributes to the Formation of the Abscission Site for Cell Division.Cells · 2019Article
- Tyr198 is the Essential Autophosphorylation Site for STK16 Localization and Kinase Activity.International journal of molecular sciences · 2019Article
- The crystal structure of the protein kinase HIPK2 reveals a unique architecture of its CMGC-insert region.The Journal of biological chemistry · 2019Article
- Article
- HIPK2 is necessary for type I interferon-mediated antiviral immunity.Science signaling · 2019Article
- Protein kinase D displays intrinsic Tyr autophosphorylation activity: insights into mechanism and regulation.FEBS letters · 2018Article
- HIPK2 and extrachromosomal histone H2B are separately recruited by Aurora-B for cytokinesis.Oncogene · 2018Article
- Effects of Y361-auto-phosphorylation on structural plasticity of the HIPK2 kinase domain.Protein science : a publication of the Protein Society · 2018Article
- HIPK2-T566 autophosphorylation diversely contributes to UV- and doxorubicin-induced HIPK2 activation.Oncotarget · 2017Article
- Arsenic-Induced Activation of the Homeodomain-Interacting Protein Kinase 2 (HIPK2) to cAMP-Response Element Binding Protein (CREB) Axis.Journal of molecular biology · 2017Article
- The DNA damage-induced cell death response: a roadmap to kill cancer cells.Cellular and molecular life sciences : CMLS · 2016Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
HIPK2 (homeodomain-interacting protein kinase-2) binds to and phosphorylates, at Ser and Thr residues, a large number of targets involved in cell division and cell fate decision in response to different physiological or stress stimuli. Inactivation of HIPK2 has been observed in human and mouse cancers supporting its role as a tumor suppressor. Despite the biological relevance of this kinase, very little is known on how HIPK2 becomes catalytically active. Based on sequence homologies, HIPK2 has been taxonomically classified as a subfamily member of the dual-specificity tyrosine-regulated kinases (DYRKs) and the activation-loop Y354 of HIPK2 has been found phosphorylated in different cells; however, the relevance of this Y phosphorylation is presently unknown. Here, we show that HIPK2, which is extensively phosphorylated at S/T sites throughout its functional domains, becomes catalytically active by autophosphorylation at the activation-loop Y354. In particular, we found that, in analogy to DYRKs, HIPK2-Y354 phosphorylation is an autocatalytic event and its prevention, through Y354 substitution with non-phosphorylatable amino acids or by using the kinase inhibitor purvalanol A, induces a strong reduction of the HIPK2 S/T-kinase activity on different substrates. Interestingly, at variance from DYRKs, inhibition of HIPK2-Y354 phosphorylation induces a strong out-of-target Y-kinase activity in cis and a strong cytoplasmic relocalization of the kinase. Together, these results demonstrate that the catalytic activity, substrate specificity, and subcellular localization of HIPK2 are regulated by autophosphorylation of its activation-loop Y354.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.