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Mitogen- and stress-activated protein kinase 1 mediates activation of Akt by ultraviolet B irradiation

M Nomura1, A Kaji, W Y Ma

  • 1Hormel Institute, University of Minnesota, 801 16th Ave. NE, Austin, MN 55912, USA.

The Journal of Biological Chemistry
|May 15, 2001
PubMed

Insights

UVB irradiation activates Akt through the Msk1 kinase pathway. This pathway involves Erk and p38 kinases, revealing a novel mechanism for UVB-induced cellular responses.

Area of Science:

  • Cellular signaling pathways
  • Molecular biology
  • Photobiology

Background:

  • Akt (protein kinase B) plays a crucial role in cellular processes.
  • UVB irradiation is known to induce cellular responses, including kinase activation.
  • The precise mechanism of UVB-induced Akt activation remains incompletely understood.

Purpose of the Study:

  • To elucidate the molecular mechanism underlying UVB-induced Akt activation in mouse epidermal JB6 cells.
  • To identify the key signaling molecules and pathways involved in this activation process.

Main Methods:

  • Utilized chemical inhibitors (LY 294002, PD 98059, SB 202190) and dominant-negative mutants for phosphatidylinositol 3-kinase (p85), Erk2, p38 kinase, and c-Jun N-terminal kinase 1 (JNK1).
  • Investigated protein phosphorylation and kinase activity through immunoprecipitation and Western blotting.
  • Assessed the role of mitogen- and stress-activated protein kinase 1 (Msk1) in UVB-induced Akt activation.

Main Results:

  • UVB-induced Akt activation was dependent on phosphatidylinositol 3-kinase (PI3K) and involved Erk and p38 kinase pathways.
  • Neither Erk nor p38 directly phosphorylated Akt; instead, mitogen- and stress-activated protein kinase 1 (Msk1) was identified as the direct activator.
  • Msk1 phosphorylated Akt at threonine 308 and serine 473, leading to its activation, and a kinase-dead Msk1 mutant blocked UVB-induced Akt activation.

Conclusions:

  • UVB-induced Akt activation is mediated by Msk1, a downstream kinase of the Erk and p38 signaling pathways.
  • This study reveals a novel signaling cascade: UVB -> Erk/p38 -> Msk1 -> Akt.
  • Understanding this pathway is crucial for comprehending cellular responses to UVB damage and developing targeted interventions.

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