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

Integrin receptor activation is an important regulatory mechanism for cell- substrate and cell-cell adhesion. In this study, we explore a signaling pat hway activated by mAb 12G10, an antibody that can activate beta (1) integri ns and induce integrin-mediated cell-cell and cell-substrate adhesion. We h ave 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 intrac ellular cAMP levels and PKA activity, and a concomitant shift in the locali zation of the PKA type II regulatory subunits from the cytoplasm to areas w here integrins expressing the 12G10 epitope are located. MAb 12G10-induced cell-cell adhesion was mimicked by a combination of clustering beta (1) int egrins and elevating PKA activity with Sp-adenosine-3',5'-cyclic monophosph orothioate or forskolin. We also show that two processes required for HT-10 80 cell-cell adhesion, integrin clustering and F-actin polymerization are b oth dependent on PKA. Taken together, our data suggest that PKA plays a key role in the signaling pathway, resulting from activation of beta (1) integ rins, and that this enzyme may be required for upregulation of cell-substra te and cell-cell adhesion.