※ NAK family introduction

    NAK family is composed of four members. Family member MPSK is a membrane-associated protein kinase that phosphorylates on serine and threonine residues. In vitro substrates include DRG1, ENO1 and EIF4EBP1. MPSK can also autophosphorylates. In addition, MPSK may be involved in secretory vesicle trafficking or intracellular signaling and may have a role in regulating stromal-epithelial interactions that occur during ductal morphogenesis in the mammary gland. AAK1, another member, regulates clathrin-mediated endocytosis by phosphorylating the AP2M1/mu2 subunit of the adaptor protein complex 2 (AP-2) which ensures high affinity binding of AP-2 to cargo membrane proteins during the initial stages of endocytosis. Isoform 1 and isoform 2 display similar levels of kinase activity towards AP2M1. AAK1 can regulate phosphorylation of other AP-2 subunits as well as AP-2 localization and AP-2-mediated internalization of ligand complexes. Phosphorylates NUMB and regulates its cellular localization, promoting NUMB localization to endosomes. Binds to and stabilizes the activated form of NOTCH1, increases its localization in endosomes and regulates its transcriptional activity (1).

Reference
1. UniProt Annotation:   STK16_HUMAN;   AAK1_HUMAN