Amyloid β protein activates PKC-δ and induces translocation of myristoylated alanine-rich C kinase substrate (MARCKS) in microglia

Masamichi Nakai, Satoshi Tanimukai, Keiko Yagi, Naoaki Saito, Taizo Taniguchi, Akira Terashima, Toshio Kawamata, Hideyuki Yamamoto, Kohji Fukunaga, Eishichi Miyamoto, Chikako Tanaka

Research output: Contribution to journalArticlepeer-review

26 Citations (Scopus)

Abstract

The increased accumulation of activated microglia containing amyloid β protein (Aβ) around senile plaques is a common pathological feature in subjects with Alzheimer's disease (AD). Much less is known, however, of intracellular signal transduction pathways for microglial activation in response to Aβ. We investigated intracellular signaling in response to Aβ stimulation in primary cultured rat microglia. We found that the kinase activity of PKC-δ but not that of PKC-α or -ε is increased by stimulation of microglia with Aβ, with a striking tyrosine phosphorylation of PKC-δ. In microglia stimulated with Aβ, tyrosine phosphorylation of PKC-δ was evident at the membrane fraction without an overt translocation of PKC-δ. PKC-δ co-immunoprecipitated with MARCKS from microglia stimulated with Aβ. Aβ induced translocation of MARCKS from the membrane fraction to the cytosolic fraction. Immunocytochemical analysis revealed that phosphorylated MARCKS accumulated in the cytoplasm, particularly at the perinuclear region in microglia treated with Aβ. Taken together with our previous observations that Aβ-induced phosphorylation of MARCKS and chemotaxis of microglia are inhibited by either tyrosine kinase or PKC inhibitors, our results provide evidence that Aβ induces phosphorylation and translocation of MARCKS through the tyrosine kinase-PKC-δ signaling pathway in microglia.

Original languageEnglish
Pages (from-to)593-600
Number of pages8
JournalNeurochemistry International
Volume38
Issue number7
DOIs
Publication statusPublished - 2001 Jun 1
Externally publishedYes

Keywords

  • Alzheimer disease
  • Amyloid β protein
  • MARCKS
  • Microglia
  • PKC-δ
  • Tyrosine kinase

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Cell Biology

Fingerprint Dive into the research topics of 'Amyloid β protein activates PKC-δ and induces translocation of myristoylated alanine-rich C kinase substrate (MARCKS) in microglia'. Together they form a unique fingerprint.

Cite this