I kappa B kinase beta phosphorylates Dok1 serines in response to TNF, IL-1, or gamma radiation

SH Lee, C Andrieu, F Saltel, O Destaing, J Auclair, V Pouchkine, J Michelon, B Salaun, R Kobayashi, P Jurdic, ED Kieff, BS Sylla

Research output: Contribution to journalArticle (Academic Journal)peer-review

Abstract

Dok1 is an abundant Ras-GTPase-activating protein-associated tyrosine kinase substrate that negatively regulates cell growth and promotes migration. We now find that lkappaB kinase beta (IKKbeta) associated with and phosphorylated Dok1 in human epithelial cells and B lymphocytes. IKKbeta phosphorylation of Dok1 depended on Dok1 S-439, S-443, S-446, and S-450. Recombinant IKKbeta also phosphorylated Dok1 or Dok1 amino acids 430-481 in vitro. TNF-alpha, IL-1, gamma radiation, or IKKbeta overexpression phosphorylated Dok1 S-443, S-446, and S-450 in vivo, as detected with Dok1 phospho-S site-specific antisera. Moreover, Dokl with 5439, 5443, 5446, and 5450 mutated to A was not phosphorylated by IKKbeta in vivo. Surprisingly, mutant Dok1 A(439), A(443), A(446), and A(450) differed from wild-type Dok1 in not inhibiting platelet-derived growth factor-induced extracellular signal-regulated kinase 1/2 phosphorylation or cell growth. Mutant Dok1 A(439), A(443), A(446), and A(450) also did not promote cell motility, whereas wild-type Dokl promoted cell motility, and Dok1 E-439, E-443, E-446, and E-450 further enhanced cell motility. These data indicate that IKKbeta phosphorylates Dok1 S439S443 and S446S450 after TNF-alpha, IL-1, or gamma-radiation and implicate the critical Dok1 serines in Dok1 effects after tyrosine kinase activation.
Translated title of the contributionI kappa B kinase beta phosphorylates Dok1 serines in response to TNF, IL-1, or gamma radiation
Original languageEnglish
Pages (from-to)17416 - 17421
JournalProceedings of the National Academy of Sciences of the United States of America
Volume101 (50)
Publication statusPublished - Dec 2004

Bibliographical note

Publisher: Natl Acad Sciences
Other identifier: IDS Number: 880QD

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