Pak1 phosphorylation enhances cortactin-N-WASP interaction in clathrin-caveolin-independent endocytosis.
Growing evidence indicates that kinases are central to the regulation of endocytic pathways. Previously, we identified p21-activated kinase 1 (Pak1) as the first specific regulator of clathrin- and caveolae-independent endocytosis used by the interleukin 2 receptor subunit (IL-2R). Here, we address the mechanism by which Pak1 regulates IL-2Rbeta endocytosis. First, we show that Pak1 phosphorylates an activator of actin polymerization, cortactin, on its serine residues 405 and 418. Consistently, we observe a specific inhibition of IL-2Rbeta endocytosis when cells overexpress a cortactin, wherein these serine residues have been mutated. In addition, we show that the actin polymerization enhancer, neuronal Wiskott-Aldrich syndrome protein (N-WASP), is involved in IL-2Rbeta endocytosis. Strikingly, we find that Pak1 phosphorylation of cortactin on serine residues 405 and 418 increases its association with N-WASP. Thus, Pak1, by controlling the interaction between cortactin and N-WASP, could regulate the polymerization of actin during clathrin-independent endocytosis.
Grassart
Alexandre
A
Unité de Biologie des Interactions Cellulaires, Institut Pasteur, CNRS URA 2582, 25 rue du Docteur Roux, 75724 Paris Cedex 15, France.
Meas-Yedid
Vannary
V
Dufour
Alexandre
A
Olivo-Marin
Jean-Christophe
JC
Dautry-Varsat
Alice
A
Sauvonnet
Nathalie
N
D051378:Actin-Related Protein 3 / Q000378:metabolism; D000199:Actins / Q000378:metabolism; D000818:Animals; D022461:Caveolins / Q000378:metabolism*; D002460:Cell Line; D002966:Clathrin / Q000378:metabolism*; D051356:Cortactin / Q000235:genetics / Q000378:metabolism*; D004705:Endocytosis / Q000502:physiology*; D006801:Humans; D053646:Interleukin-2 Receptor beta Subunit / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012694:Serine / Q000378:metabolism; D051317:Wiskott-Aldrich Syndrome Protein, Neuronal / Q000235:genetics / Q000378:metabolism*; D054462:p21-Activated Kinases / Q000235:genetics / Q000378:metabolism*
D051378:Actin-Related Protein 3; D000199:Actins; D022461:Caveolins; D002966:Clathrin; D051356:Cortactin; D053646:Interleukin-2 Receptor beta Subunit; D034741:RNA, Small Interfering; D011993:Recombinant Fusion Proteins; D051317:Wiskott-Aldrich Syndrome Protein, Neuronal; D012694:Serine; D054462:p21-Activated Kinases