p38 mitogen-activated protein kinase can be involved in transforming growth factor beta superfamily signal transduction in Drosophila wing morphogenesis

p38 mitogen-activated protein kinase (p38) has been extensively studied as a stress-responsive kinase, but its role in development remains unknown. Th e fruit fly, Drosophila melanogaster, has two p38 genes, D-p38a and D-p38b. To elucidate the developmental function of the Drosophila p38's, we used v arious genetic and pharmacological manipulations to interfere with their fu nctions: expression of a dominant-negative form of D-p38b, expression of an tisense D-p38b RNA, reduction of the D-p38 gene dosage, and treatment with the p38 inhibitor SB203580. Expression of a dominant-negative D-p38b in the wing imaginal disc caused a decapentaplegic (dpp)-like phenotype and enhan ced the phenotype of a dpp mutant. Dpp is a secretory ligand belonging to t he transforming growth factor beta superfamily which triggers various morph ogenetic processes through interaction with the receptor Thick veins (Tkv). Inhibition of D-p38b function also caused the suppression of the wing phen otype induced by constitutively active Tkv (Tkv(CA)). Mosaic analysis revea led that D-p38b regulates the Tkv-dependent transcription of the optomotor- blind (omb) gene in non-Dpp-producing cells, indicating that the site of D- p38b action is downstream of Tkv. Furthermore, forced expression of Tkv(CA) induced an increase in the phosphorylated active form(s) of D-p38(s). Thes e results demonstrate that p38, in addition to its role as a transducer of emergency stress signaling, may function to modulate Dpp signaling.