9cbc2f4bed31ca208261d92b7694d60d pmc_10216758.pdf 329a6f025ec286af50f97ea217cfaf2dcb8a8aac pmc_10216758.pdf da619f8c8deed536080430820b453de46ffa96c4a296fd8b0d0d6c877d474781 pmc_10216758.pdf Title: The Phosphorylation of Kv1.3: A Modulatory Mechanism for a Multifunctional Ion Channel Subject: The voltage-gated potassium channel Kv1.3 plays a pivotal role in a myriad of biological processes, including cell proliferation, differentiation, and apoptosis. Kv1.3 undergoes fine-tuned regulation, and its altered expression or function correlates with tumorigenesis and cancer progression. Moreover, posttranslational modifications (PTMs), such as phosphorylation, have evolved as rapid switch-like moieties that tightly modulate channel activity. In addition, kinases are promising targets in anticancer therapies. The diverse serine/threonine and tyrosine kinases function on Kv1.3 and the effects of its phosphorylation vary depending on multiple factors. For instance, Kv1.3 regulatory subunits (KCNE4 and Kv) can be phosphorylated, increasing the complexity of channel modulation. Scaffold proteins allow the Kv1.3 channelosome and kinase to form protein complexes, thereby favoring the attachment of phosphate groups. This review compiles the network triggers and signaling pathways that culminate in Kv1.3 phosphorylation. Alterations to Kv1.3 expression and its phosphorylation are detailed, emphasizing the importance of this channel as an anticancer target. Overall, further research on Kv1.3 kinase-dependent effects should be addressed to develop effective antineoplastic drugs while minimizing side effects. This promising field encourages basic cancer research while inspiring new therapy development. Keywords: K+ channels; cancer; phosphorylation Author: María Navarro-Pérez, Irene Estadella, Anna Benavente-Garcia, Ruth Orellana-Fernández, Anna Petit, Joan Carles Ferreres and Antonio Felipe Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Thu May 11 12:01:39 2023 CEST ModDate: Thu May 11 12:07:21 2023 CEST Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 21 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 1005285 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- YALSGE+VnURWPalladioL Type 1 Custom yes yes no 10 0 ITBGYM+EURM10 Type 1 Builtin yes yes no 15 0 PBNISN+URWPalladioL-Bold Type 1 Custom yes yes no 19 0 DDWAPZ+URWPalladioL-Roma Type 1 Custom yes yes no 24 0 QOAWTE+URWPalladioL-Ital Type 1 Custom yes yes no 28 0 IOJCNK+VnURWPalladioL-Bold Type 1 Custom yes yes no 32 0 LCJEVJ+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 51 0 FXXUVH+CMSY10 Type 1 Builtin yes yes no 82 0 CRJHCU+PazoMath-Italic Type 1 Builtin yes yes no 108 0 GNJIKN+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 124 0 GNJIKO+PalatinoLinotype CID TrueType Identity-H yes yes yes 127 0 GNJIKP+PalatinoLinotype TrueType WinAnsi yes yes no 133 0 GNJILB+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 136 0 GNJJIN+PalatinoLinotype TrueType MacRoman yes yes no 139 0 Jhove (Rel. 1.22.1, 2019-04-17) Date: 2023-07-22 02:39:02 CEST RepresentationInformation: pmc_10216758.pdf ReportingModule: PDF-hul, Rel. 1.12.1 (2019-04-17) LastModified: 2023-07-20 02:26:43 CEST Size: 1005285 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 653 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@44c8afef Item: Title: Phosphorylation Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7b69c6ba Item: Title: Kv1.3 Phosphorylation Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@46daef40 Children: Item: Title: Kv1.3 Ser/Thr Kinases Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@12f41634 Children: Item: Title: PKA Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@13c27452 Item: Title: PKC Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@262b2c86 Item: Title: SGK1 Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@371a67ec Item: Title: ERK1/2 Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@5ed828d Item: Title: Kv1.3 Tyr Kinases Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@50d0686 Children: Item: Title: MAPK Family Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7a3d45bd Item: Title: Src Family Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1e7c7811 Item: Title: Receptor Tyrosine Kinases (RTKs) Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77ec78b9 Item: Title: Scaffolding Proteins Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1a3869f4 Item: Title: Phosphorylation of Regulatory Subunits Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@a38d7a3 Children: Item: Title: Kv Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77f99a05 Item: Title: KCNEs Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@63440df3 Item: Title: Functional Consequences of Kv1.3 Phosphorylation Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@3aeaafa6 Item: Title: Conclusions Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@76a3e297 Item: Title: References Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@4d3167f4 Info: Title: The Phosphorylation of Kv1.3: A Modulatory Mechanism for a Multifunctional Ion Channel Author: María Navarro-Pérez, Irene Estadella, Anna Benavente-Garcia, Ruth Orellana-Fernández, Anna Petit, Joan Carles Ferreres and Antonio Felipe Subject: The voltage-gated potassium channel Kv1.3 plays a pivotal role in a myriad of biological processes, including cell proliferation, differentiation, and apoptosis. Kv1.3 undergoes fine-tuned regulation, and its altered expression or function correlates with tumorigenesis and cancer progression. Moreover, posttranslational modifications (PTMs), such as phosphorylation, have evolved as rapid switch-like moieties that tightly modulate channel activity. In addition, kinases are promising targets in anticancer therapies. The diverse serine/threonine and tyrosine kinases function on Kv1.3 and the effects of its phosphorylation vary depending on multiple factors. For instance, Kv1.3 regulatory subunits (KCNE4 and Kv) can be phosphorylated, increasing the complexity of channel modulation. Scaffold proteins allow the Kv1.3 channelosome and kinase to form protein complexes, thereby favoring the attachment of phosphate groups. This review compiles the network triggers and signaling pathways that culminate in Kv1.3 phosphorylation. Alterations to Kv1.3 expression and its phosphorylation are detailed, emphasizing the importance of this channel as an anticancer target. Overall, further research on Kv1.3 kinase-dependent effects should be addressed to develop effective antineoplastic drugs while minimizing side effects. This promising field encourages basic cancer research while inspiring new therapy development. 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