PKCι

PKCι (PRKCI) is an atypical serine/threonine protein kinase that supports epithelial cell polarity, proliferation, survival, and stem/progenitor-cell control^[1][2]. Mechanistically, PRKCI links polarity signaling to Notch-dependent stem/progenitor expansion, and loss of Prkci increased multiple stem/progenitor populations through NUMB inactivation and NOTCH1 activation^[2]. In cancer models, PKCι supports Ras-mediated transformation and colon carcinogenesis through a Ras-PKCι-Rac1 axis^[3]. In lung squamous cell carcinoma, PRKCI and SOX2 are coamplified, and PKCι phosphorylates SOX2 to activate HHAT/Hedgehog signaling and maintain a stem-like phenotype^[4]. Compared with the related atypical isoform PKCζ, PKCι shows distinct, non-overlapping cancer functions; in NSCLC cells, PKCι is highly expressed whereas PKCζ is undetectable^[5][6]. For experimental applications, aurothiomalate and related gold compounds disrupt PKCι-Par6 PB1-domain interactions, block PKCι-dependent Rac1 signaling, and inhibit transformed growth in NSCLC models^[7][8]. Fragment-based discovery has also produced potent PKCι inhibitors, supporting chemical-probe development for isoform-focused pathway studies^[9].