Protein kinase C-related kinase 1 and 2 play an essential role in thromboxane-mediated neoplastic responses in prostate cancer

摘要: // Aine G. O’Sullivan 1, * , Eamon P. Mulvaney Paula B. Hyland 1 Therese Kinsella UCD School of Biomolecular and Biomedical Sciences, Conway Institute Research, University College Dublin, Belfield, Ireland These authors have contributed equally to this work Correspondence to: Kinsella, e-mail: therese.kinsella@ucd.ie Keywords: thromboxane, receptor, cancer, prostate, protein kinase C-related Received: May 01, 2015      Accepted: July 06, Published: 20, 2015 ABSTRACT The prostanoid thromboxane (TX) A 2 is increasingly implicated in neoplastic progression, including prostate cancer (PCa). Mechanistically, we recently identified (PRK) as a functional interactant both the TPα TPβ isoforms human T receptor (TP). interaction with PRK1 was not only essential for TPα/TPβ-induced PCa cell migration but also enabled TXA -TP axis induce phosphorylation histone H3 at Thr11 (H3Thr11), an epigenetic marker previously exclusively associated androgen-induced chromatin remodelling transcriptional activation. member subfamily three structurally related kinases comprising PRK1/PKNα, PRK2/PKNγ PRK3/PKNβ that are widely yet differentially various cancers. Hence, focusing on setting study investigated whether and/or might complex PRK2 PRK3 regulate their activity responses. While were found immune complexes PRK1, activation signalling, they do so TP agonist-regulated manner dependent T-loop status PRKs independent activity. Furthermore, -mediated responses adenocarcinoma PC-3 cells, H3Thr11 phosphorylation, occur through PRK1- PRK2-, PRK3-, mechanism. Collectively, these data suggest acts regulator provides mechanistic explanation, least part, prophylactic benefits Aspirin reducing risk certain