Function of protein kinase A in hedgehog signal transduction and Drosophila imaginal disc development

Abstract

Reduced protein kinase A (PKA) activity in anterior imaginal disc cells leads to cell-autonomous induction of decapentaplegic (dpp), wingless (wg), and patched (ptc) transcription that is independent of hedgehog (hh) gene activity. The resulting nonautonomous adult wing and leg pattern duplications are largely due to induced dpp and wg expression and resemble phenotypes elicited by ectopic hh expression. Inhibition of PKA in anterior cells close to the posterior compartment can substitute for hh activity to promote growth of imaginal discs, whereas overexpression of PKA can counteract transcriptional induction of ptc by hh in these cells. PKA therefore appears to be an integral component of the mechanism by which hh regulates the expression of key patterning molecules in imaginal discs.

Sonic Hedgehog Promotes Rod Photoreceptor Differentiation in Mammalian Retinal CellsIn Vitro

“…A current model holds that hedgehog activates decapentaplegic and wingless expression in wing and leg disks by reversing a tonic PK A-mediated inhibition of these genes (Felsenfeld and Kennison, 1995;Jiang and Struhl, 1995;Li et al, 1995;Strutt et al, 1995;Hammerschmidt et al, 1996). Data from vertebrate studies also support this model: the SHH-mediated induction of dopaminergic neurons in the ventral mesencephalon was blocked by increasing the level of PK A activity with forskolin or 8-bromo-cyclic AM P (cAM P) (Hynes et al, 1995).…”

“…Because SHH-N stimulates retinal progenitor cell proliferation, it is possible that SHH-N also induces progenitor cells to differentiate into rod photoreceptors. This is analogous to the actions of hedgehog in Drosophila eye disks, in which hedgehog expression also regulates photoreceptor differentiation at the morphogenetic furrow (Jiang and Struhl, 1995;Li et al, 1995;Strutt et al, 1995). It is also possible, however, that hedgehog proteins act later in photoreceptor differentiation.…”

Synaptic neuropeptide release induced by octopamine without Ca 2+ entry into the nerve terminal

“…However, there are two limitations associated with bath applied H89: it could have acted on both sides of the synapse or had nonspecific effects in addition to inhibiting PKA. Therefore, a selective dominant-negative regulatory PKA subunit (20) was expressed only in neurons to specifically inhibit presynaptic PKA. With two chromosomal insertions of the dominant-negative gene (BDK22 and BDK35), octopamine-induced release was inhibited (Fig.…”

Regulation of Wnt5a expression in human mammary cells by protein kinase C activity and the cytoskeleton

“…The wingless (WG) signal is via dishevelled and zeste white 3 (the Drosophila homologue of glycogen synthase kinase) involving hedgehog and patched. The latter pathway is modified by PKA and WG expression in the responding cells (Li et al, 1995). Thus, steps in this pathway may be involved in paracrine regulation of human Wnts during cell density changes.…”