Regulation of lung epithelial cell morphology by cAMP-dependent protein kinase type I isozyme

Cell shape is mediated in part by the actin cytoskeleton and the actin-bind ing protein vinculin. These proteins in turn are regulated by protein phosp horylation. We assessed the contribution of cAMP-dependent protein kinase A isozyme I (PKA I) to lung epithelial morphology using the E10/E9 sibling c ell lines. PKA I concentration is high in flattened, nontumorigenic E10 cel ls but low in their round E9 transformants. PKA I activity was lowered in E 10 cells by stable transfection with a dominant negative RI alpha mutant of the PKA I regulatory subunit and was raised in E9 cells by stable transfec tion with a wild-type Ca catalytic subunit construct. Reciprocal changes in morphology ensued. E10 cells became rounder and grew in colonies, their ac tin microfilaments were disrupted, and vinculin localization at cell-cell j unctions was diminished. The converse occurred in E9 cells on elevating the ir PKA I content. Demonstration that PKA I is responsible for the dichotomy in these cellular behaviors suggests that manipulating PKA I concentration s in lung cancer would provide useful adjuvant therapy.