Current thoughts on cellular functions of numb-associated kinases

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 Numbassociated 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.

Numb-associated kinases regulate sandfly-borne Toscana virus entry

“…This, however, might be different with TOSV and Rabies, where knockdown of AAK1 and GAK showed different results. One explanation for this difference is additional non-redundant functions attributed to these kinases [ 12 , 47 ]. Thus, further studies addressing this point might reveal additional details about TOSV entry and the roles of AAK1 and GAK.…”

“…These kinases were shown to phosphorylate AP2 on Threonine 156 [ 10 , 11 ]. AAK1 and GAK have additional non-redundant roles in endocytosis and other pathways (reviewed in [ 12 ]). AAK1 and GAK were shown to mediate the entry of multiple viruses [ 13–19 ], highlighting them as potential broad-spectrum antiviral targets.…”