title: POPX2 phosphatase regulates the KIF3 kinesin motor complex.
abstract: The kinesin motors are important in the regulation of cellular functions such as protein trafficking, spindle organization and centrosome separation. In this study, we have identified POPX2, a serine-threonine phosphatase, as an interacting partner of the KAP3 subunit of the kinesin-2 motor. The kinesin-2 motor is a heterotrimeric complex composed of KIF3A, KIF3B motor subunits and KAP3, the non-motor subunit, which binds the cargo. Here we report that the phosphatase POPX2 is a negative regulator of the trafficking of N-cadherin and other cargoes; consequently, it markedly influences cell-cell adhesion. POPX2 affects trafficking by determining the phosphorylation status of KIF3A at serine 690. This is consistent with the observation that the KIF3A-S690A mutant is defective in cargo trafficking. Our studies also implicate CaMKII as the kinase that phosphorylates KIF3A at serine 690. These results strongly suggest that POPX2 and CaMKII are a phosphatase-kinase pair that regulates kinesin-mediated transport and cell-cell adhesion.
authors: School of Biological Sciences, College of Science, Nanyang Technological University, 637551 Singapore.
authors: Hui-Qun
authors: HQ
authors: Phang
authors: Jing-Ling
authors: JL
authors: Hoon
authors: Soak-Kuan
authors: SK
authors: Lai
authors: Yukai
authors: Y
authors: Zeng
authors: Keng-Hwee
authors: KH
authors: Chiam
authors: Hoi-Yeung
authors: HY
authors: Li
authors: Cheng-Gee
authors: CG
authors: Koh
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D019556:COS Cells; D015820:Cadherins / Q000378:metabolism; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism; D002448:Cell Adhesion; D002522:Chlorocebus aethiops; D017124:Conserved Sequence; D006367:HeLa Cells; D006801:Humans; D016547:Kinesins / Q000737:chemistry / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D041681:NIH 3T3 Cells; D010749:Phosphoprotein Phosphatases / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D025941:Protein Interaction Mapping; D011499:Protein Processing, Post-Translational; D021381:Protein Transport; D051176:beta Catenin / Q000378:metabolism
chemical_list: D015703:Antigens, CD; C050361:CDH2 protein, human; C495270:CTNNB1 protein, human; D015820:Cadherins; C087415:KIF3A protein, human; D051176:beta Catenin; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; C459194:PPM1F protein, human; D010749:Phosphoprotein Phosphatases; D016547:Kinesins
keywords: Calcium-calmodulin kinase; Kinesin-2 motor; N-cadherin; POPX2 phosphatase