title: RSK2 protein suppresses integrin activation and fibronectin matrix assembly and promotes cell migration.
abstract: Modulation of integrin activation is important in many cellular functions including adhesion, migration, and assembly of the extracellular matrix. RSK2 functions downstream of Ras/Raf and promotes tumor cell motility and metastasis. We therefore investigated whether RSK2 affects integrin function. We report that RSK2 mediates Ras/Raf inactivation of integrins. As a result, we find that RSK2 impairs cell adhesion and integrin-mediated matrix assembly and promotes cell motility. Active RSK2 appears to affect integrins by reducing actin stress fibers and disrupting focal adhesions. Moreover, RSK2 co-localizes with the integrin activator talin and is present at integrin cytoplasmic tails. It is thereby in a position to modulate integrin activation and integrin-mediated migration. Activation of RSK2 promotes filamin phosphorylation and binding to integrins. We also find that RSK2 is activated in response to integrin ligation to fibronectin. Thus, RSK2 could participate in a feedback loop controlling integrin function. These results reveal RSK2 as a key regulator of integrin activity and provide a novel mechanism by which it may promote cell migration and cancer metastasis.
authors.affiliation: Cancer Biology Program, University of Hawaii Cancer Center, Honolulu, Hawaii 96813, USA.
authors.forename: Joanna E
authors.initials: JE
authors.lastname: Gawecka
authors.forename: Shirley S
authors.initials: SS
authors.lastname: Young-Robbins
authors.forename: Florian J
authors.initials: FJ
authors.lastname: Sulzmaier
authors.forename: Maisel J
authors.initials: MJ
authors.lastname: Caliva
authors.forename: Minna M
authors.initials: MM
authors.lastname: Heikkilä
authors.forename: Michelle L
authors.initials: ML
authors.lastname: Matter
authors.forename: Joe W
authors.initials: JW
authors.lastname: Ramos
mesh_terms: D000818:Animals; D016466:CHO Cells; D002448:Cell Adhesion / Q000502:physiology; D002465:Cell Movement / Q000502:physiology*; D003285:Contractile Proteins / Q000235:genetics / Q000378:metabolism; D006224:Cricetinae; D003412:Cricetulus; D004789:Enzyme Activation / Q000502:physiology; D064448:Filamins; D006367:HeLa Cells; D006801:Humans; D016023:Integrins / Q000235:genetics / Q000378:metabolism*; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation / Q000502:physiology; D038744:Ribosomal Protein S6 Kinases, 90-kDa / Q000235:genetics / Q000378:metabolism*; D016608:Talin / Q000235:genetics / Q000378:metabolism; D048490:raf Kinases / Q000235:genetics / Q000378:metabolism; D018631:ras Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D003285:Contractile Proteins; D064448:Filamins; D016023:Integrins; D008840:Microfilament Proteins; D016608:Talin; D038744:Ribosomal Protein S6 Kinases, 90-kDa; D048490:raf Kinases; C069330:ribosomal protein S6 kinase, 90kDa, polypeptide 3; D018631:ras Proteins