Current thoughts on cellular functions of numb-associated kinases

Mol Biol Rep. 2023 May;50(5):4645-4652. doi: 10.1007/s11033-023-08372-x. Epub 2023 Apr 4.

Abstract

Members of the Numb-associated kinase family of serine/threonine kinases play an essential role in many cellular processes, such as endocytosis, autophagy, dendrite morphogenesis, osteoblast differentiation, and the regulation of the Notch pathway. Numb-associated kinases have been relevant to diverse diseases, including neuropathic pain, Parkinson's disease, and prostate cancer. Therefore, they are considered potential therapeutic targets. In addition, it is reported that Numb-associated kinases have been involved in the life cycle of multiple viruses such as hepatitis C virus (HCV), Ebola virus (EBOV), and dengue virus (DENV). Recently, Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to threaten global health. Studies show that Numb-associated kinases are implicated in the infection of SARS-CoV-2 which can be suppressed by Numb-associated kinases inhibitors. Thus, Numb-associated kinases are proposed as potential host targets for broad-spectrum antiviral strategies. We will focus on the recent advances in Numb-associated kinases-related cellular functions and their potential as host targets for viral infections in this review. Questions that remained unknown on the cellular functions of Numb-associated kinases will also be discussed.

Keywords: AAK1; Autophagy; COVID-19; Endocytosis; NAK.

Publication types

  • Review

MeSH terms

  • Antiviral Agents
  • COVID-19*
  • Endocytosis
  • Hepatitis C*
  • Humans
  • Male
  • Membrane Proteins / metabolism
  • Nerve Tissue Proteins / metabolism
  • Protein Serine-Threonine Kinases / metabolism
  • SARS-CoV-2 / metabolism

Substances

  • Protein Serine-Threonine Kinases
  • Antiviral Agents
  • NUMB protein, human
  • Membrane Proteins
  • Nerve Tissue Proteins