PKC-dependent human monocyte adhesion requires AMPK and Syk activation

Mei Ying Chang, Duen Yi Huang, Feng Ming Ho, Kuo Chin Huang, Wan Wan Lin

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

PKC plays a pivotal role in mediating monocyte adhesion; however, the underlying mechanisms of PKC-mediated cell adhesion are still unclear. In this study, we elucidated the signaling network of phorbol ester PMA-stimulated human monocyte adhesion. Our results with pharmacological inhibitors suggested the involvement of AMPK, Syk, Src and ERK in PKC-dependent adhesion of THP-1 monocytes to culture plates. Biochemical analysis further confirmed the ability of PMA to activate these kinases, as well as the involvement of AMPK-Syk-Src signaling in this event. Direct protein interaction between AMPK and Syk, which requires the kinase domain of AMPK and linker region of Syk, was observed following PMA stimulation. Notably, we identified Syk as a novel downstream target of AMPK; AICAR can induce Syk phosphorylation at Ser178 and activation of this kinase. However, activation of AMPK alone, either by stimulation with AICAR or by overexpression, is not sufficient to induce monocyte adhesion. Studies further demonstrated that PKC-mediated ERK signaling independent of AMPK activation is also involved in cell adhesion. Moreover, AMPK, Syk, Src and ERK signaling were also required for PMA to induce THP-1 cell adhesion to endothelial cells as well as to induce adhesion response of human primary monocytes. Taken together, we propose a bifurcated kinase signaling pathway involved in PMA-mediated adhesion of monocytes. PKC can activate LKB1/AMPK, leading to phosphorylation and activation of Syk, and subsequent activation of Src and FAK. In addition, PKC-dependent ERK activation induces a coordinated signal for cytoskeleton rearrangement and cell adhesion. For the first time we demonstrate Syk as a novel substrate target of AMPK, and shed new light on the role of AMPK in monocyte adhesion, in addition to its well identified functions in energy homeostasis.

Original languageEnglish
Article numbere40999
JournalPLoS One
Volume7
Issue number7
DOIs
Publication statusPublished - Jul 25 2012

Fingerprint

AMP-activated protein kinase
AMP-Activated Protein Kinases
monocytes
adhesion
Monocytes
Adhesion
Chemical activation
Cell adhesion
Cell Adhesion
mitogen-activated protein kinase
cell adhesion
phosphotransferases (kinases)
Phosphorylation
Phosphotransferases
phosphorylation
Endothelial cells
Phorbol Esters
Cytoskeleton
cytoskeleton
endothelial cells

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Chang, M. Y., Huang, D. Y., Ho, F. M., Huang, K. C., & Lin, W. W. (2012). PKC-dependent human monocyte adhesion requires AMPK and Syk activation. PLoS One, 7(7), [e40999]. https://doi.org/10.1371/journal.pone.0040999

PKC-dependent human monocyte adhesion requires AMPK and Syk activation. / Chang, Mei Ying; Huang, Duen Yi; Ho, Feng Ming; Huang, Kuo Chin; Lin, Wan Wan.

In: PLoS One, Vol. 7, No. 7, e40999, 25.07.2012.

Research output: Contribution to journalArticle

Chang, MY, Huang, DY, Ho, FM, Huang, KC & Lin, WW 2012, 'PKC-dependent human monocyte adhesion requires AMPK and Syk activation', PLoS One, vol. 7, no. 7, e40999. https://doi.org/10.1371/journal.pone.0040999
Chang, Mei Ying ; Huang, Duen Yi ; Ho, Feng Ming ; Huang, Kuo Chin ; Lin, Wan Wan. / PKC-dependent human monocyte adhesion requires AMPK and Syk activation. In: PLoS One. 2012 ; Vol. 7, No. 7.
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