Developmental growth and patterning are regulated by an interconnected signalling network of several pathways. In , the Warts (Wts) kinase, a component of the Hippo signalling pathway, plays an essential role in regulating transcription and growth by phosphorylating its substrate Yorkie (Yki). The phosphorylation of Yki critically influences its localisation and activity as a transcriptional coactivator. In this study, we identified the homeodomain-interacting protein kinase (Hipk) as another kinase that phosphorylates Yki and mapped several sites of Yki phosphorylated by Hipk, using in vitro analysis: Ser168, Ser169/Ser172 and Ser255. These sites might provide auxiliary input for Yki regulation in vivo, as transgenic flies with mutations in these show prominent phenotypes; Hipk, therefore, represents an additional upstream regulator of Yki that works in concert with Wts.
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http://dx.doi.org/10.3390/ijms22041862 | DOI Listing |
Clin Rheumatol
January 2025
Department of Rheumatology, Shanghai Guanghua Hospital of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Pharmaceuticals (Basel)
October 2024
Department of Medicinal Chemistry, Xiangya School of Pharmaceutical Sciences, Central South University, Changsha 410013, China.
Homeodomain-interacting protein kinase 2 (HIPK2) is critically involved in the progression of renal fibrosis. This study aims to identify and characterize a novel HIPK2 inhibitor, CHR-6494, and investigate its therapeutic potential. Using structure-based virtual screening and molecular dynamics simulations, we identified CHR-6494 as a potent HIPK2 inhibitor with an IC of 0.
View Article and Find Full Text PDFJ Exp Clin Cancer Res
September 2024
Unit of Cellular Networks and Molecular Therapeutic Targets, IRCCS Regina Elena National Cancer Institute, Rome, Italy.
Background: Pancreatic ductal adenocarcinoma (PDAC) features KRAS mutations in approximately 90% of human cases and excessive stromal response, termed desmoplastic reaction. Oncogenic KRAS drives pancreatic carcinogenesis by acting on both epithelial cells and tumor microenvironment (TME). We have previously shown that Homeodomain-Interacting Protein Kinase 2 (HIPK2) cooperates with KRAS in sustaining ERK1/2 phosphorylation in human colorectal cancers.
View Article and Find Full Text PDFInt Immunopharmacol
November 2024
Department of Pharmacy, Xinxiang Central Hospital, The Fourth Clinical College of Xinxiang Medical University, Xinxiang 453000, Henan, China; School of Integrated Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu, China. Electronic address:
Background: Depression is a common mental illness with more than 280 million sufferers worldwide. Inflammation, particularly the c-Jun amino-terminal kinase (JNK) pathway, contributes to depression development and neuronal apoptosis. Gardenia is a herb with therapeutic effects on depression that has been shown to inhibit neuronal apoptosis.
View Article and Find Full Text PDFArch Physiol Biochem
December 2024
Department of Colorectal Surgery, The Affiliated TCM Hospital of Guangzhou Medical University, Guangzhou, China.
Background: This study aimed to explore the molecular mechanism of homeodomain-interacting protein kinase 2 (HIPK2) in diabetic foot ulcers (DFU).
Methods: High glucose (HG)-induced human umbilical vein endothelial cells (HUVECs) were used to construct DFU cell models. Cell functions were determined using CCK8 assay, EdU assay, flow cytometry, transwell assay, wound healing assay and tube formation assay.
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