Positive regulation of cell-cell and cell-substrate adhesion by protein kinase A

J Cell Sci. 2001 Sep;114(Pt 18):3265-72. doi: 10.1242/jcs.114.18.3265.

Abstract

Integrin receptor activation is an important regulatory mechanism for cell-substrate and cell-cell adhesion. In this study, we explore a signaling pathway activated by mAb 12G10, an antibody that can activate beta(1) integrins and induce integrin-mediated cell-cell and cell-substrate adhesion. We have found that the cAMP-dependent protein kinase (PKA) is required for both mAb 12G10-induced cell-cell and cell-substrate adhesion of HT-1080 cells. Binding of mAb 12G10 to beta(1) integrins stimulates an increase in intracellular cAMP levels and PKA activity, and a concomitant shift in the localization of the PKA type II regulatory subunits from the cytoplasm to areas where integrins expressing the 12G10 epitope are located. MAb 12G10-induced cell-cell adhesion was mimicked by a combination of clustering beta(1) integrins and elevating PKA activity with Sp-adenosine-3',5'-cyclic monophosphorothioate or forskolin. We also show that two processes required for HT-1080 cell-cell adhesion, integrin clustering and F-actin polymerization are both dependent on PKA. Taken together, our data suggest that PKA plays a key role in the signaling pathway, resulting from activation of beta(1) integrins, and that this enzyme may be required for upregulation of cell-substrate and cell-cell adhesion.

MeSH terms

  • Actins / drug effects
  • Actins / metabolism*
  • Antibodies, Monoclonal / metabolism*
  • Antibodies, Monoclonal / pharmacology
  • Cell Adhesion / physiology*
  • Cyclic AMP / agonists
  • Cyclic AMP / metabolism*
  • Cyclic AMP-Dependent Protein Kinase RIIalpha Subunit
  • Cyclic AMP-Dependent Protein Kinase RIIbeta Subunit
  • Cyclic AMP-Dependent Protein Kinase Type II
  • Cyclic AMP-Dependent Protein Kinases / drug effects
  • Cyclic AMP-Dependent Protein Kinases / metabolism*
  • Cytoplasm / metabolism
  • Fibrosarcoma / metabolism
  • Humans
  • Integrin beta1 / drug effects
  • Integrin beta1 / metabolism*
  • Tumor Cells, Cultured / metabolism

Substances

  • Actins
  • Antibodies, Monoclonal
  • Cyclic AMP-Dependent Protein Kinase RIIalpha Subunit
  • Cyclic AMP-Dependent Protein Kinase RIIbeta Subunit
  • Integrin beta1
  • PRKAR2A protein, human
  • PRKAR2B protein, human
  • Cyclic AMP
  • Cyclic AMP-Dependent Protein Kinase Type II
  • Cyclic AMP-Dependent Protein Kinases