Jd. Whittard et Sk. Akiyama, Positive regulation of cell-cell and cell-substrate adhesion by protein kinase A, J CELL SCI, 114(18), 2001, pp. 3265-3272
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.