title: The Nck-interacting kinase NIK increases Arp2/3 complex activity by phosphorylating the Arp2 subunit.
abstract: The nucleating activity of the Arp2/3 complex promotes the assembly of branched actin filaments that drive plasma membrane protrusion in migrating cells. Arp2/3 complex binding to nucleation-promoting factors of the WASP and WAVE families was previously thought to be sufficient to increase nucleating activity. However, phosphorylation of the Arp2 subunit was recently shown to be necessary for Arp2/3 complex activity. We show in mammary carcinoma cells that mutant Arp2 lacking phosphorylation assembled with endogenous subunits and dominantly suppressed actin filament assembly and membrane protrusion. We also report that Nck-interacting kinase (NIK), a MAP4K4, binds and directly phosphorylates the Arp2 subunit, which increases the nucleating activity of the Arp2/3 complex. In cells, NIK kinase activity was necessary for increased Arp2 phosphorylation and plasma membrane protrusion in response to epidermal growth factor. NIK is the first kinase shown to phosphorylate and increase the activity of the Arp2/3 complex, and our findings suggest that it integrates growth factor regulation of actin filament dynamics.
authors.affiliation: Department of Cell and Tissue Biology, University of California, San Francisco, San Francisco, CA 94143 Department of Biochemistry and Molecular Biology, University of South Alabama, Mobile, AL 36688 leclaire@southalabama.edu.
authors.forename: Lawrence L
authors.initials: LL
authors.lastname: LeClaire
authors.affiliation: Department of Cell and Tissue Biology, University of California, San Francisco, San Francisco, CA 94143.
authors.forename: Manish
authors.initials: M
authors.lastname: Rana
authors.affiliation: Department of Cell and Tissue Biology, University of California, San Francisco, San Francisco, CA 94143 Neuro-Oncology Laboratory, Infectious Diseases and Cancer Research, University of Children's Hospital Zürich, Zürich, Switzerland CH-8008.
authors.forename: Martin
authors.initials: M
authors.lastname: Baumgartner
authors.affiliation: Department of Cell and Tissue Biology, University of California, San Francisco, San Francisco, CA 94143.
authors.forename: Diane L
authors.initials: DL
authors.lastname: Barber
mesh_terms: D051377:Actin-Related Protein 2 / Q000378:metabolism*; D000199:Actins / Q000737:chemistry; D000818:Animals; D045744:Cell Line, Tumor; D048430:Cell Shape; D007700:Kinetics; D010766:Phosphorylation; D055503:Protein Multimerization; D011499:Protein Processing, Post-Translational; D017346:Protein Serine-Threonine Kinases / Q000502:physiology*; D021122:Protein Subunits / Q000378:metabolism; D011554:Pseudopodia / Q000378:metabolism; D051381:Rats; D000097782:NF-kappaB-Inducing Kinase
chemical_list: D051377:Actin-Related Protein 2; D000199:Actins; D017346:Protein Serine-Threonine Kinases; D021122:Protein Subunits; D000097782:NF-kappaB-Inducing Kinase