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Target Concepts:
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Query: UNIPROT:P41181 (
collecting duct
)
5,183
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Protein kinase A (PKA) regulates morphogenetic responses to bone morphogenetic proteins (BMPs) during embryogenesis. However, the mechanisms by which PKA regulates BMP function are unknown. During kidney development, BMP-2 and high doses of
BMP-7
inhibit branching morphogenesis, whereas low doses of
BMP-7
are stimulatory (Piscione, T. D., Yager, T. D., Gupta, I. R., Grinfeld, B., Pei, Y., Attisano, L., Wrana, J. L., and Rosenblum, N. D. (1997) Am. J. Physiol. 273, F961-F975). We examined the interactions between PKA and these BMPs in embryonic kidney explants and in the mouse inner medullary
collecting duct
-3 model of
collecting duct
morphogenesis. H-89, an inhibitor of PKA, stimulated branching morphogenesis and enhanced the stimulatory effect of low doses of
BMP-7
on tubule formation. Furthermore, H-89 rescued the inhibition of tubulogenesis by BMP-2 (or high doses of
BMP-7
) by attenuating BMP-2-induced
collecting duct
apoptosis. In contrast, 8-bromo-cAMP, an activator of PKA, inhibited tubule formation and attenuated the stimulatory effects of low doses of
BMP-7
. To determine mechanisms underlying the interdependence of BMP signaling and PKA activity, we examined the effect of PKA on the known signaling events in the BMP-2-dependent Smad1 signaling pathway and the effect of BMP-2 on PKA activity. PKA did not induce endogenous Smad1 phosphorylation, Smad1-Smad4 complex formation, or Smad1 nuclear translocation. In contrast, BMP-2 increased endogenous PKA activity and induced phosphorylation of the PKA effector, cAMP-response element-binding protein, in a PKA-dependent manner. We conclude that BMP-2 induces activation of PKA and that PKA regulates the effects of BMPs on
collecting duct
morphogenesis without activating the known signaling events in the BMP-2-dependent Smad1 signaling pathway.
...
PMID:Protein kinase A is a negative regulator of renal branching morphogenesis and modulates inhibitory and stimulatory bone morphogenetic proteins. 1047 86
The urinary
collecting duct
system of the permanent kidney develops by growth and branching of an initially unbranched epithelial tubule, the ureteric bud. Formation of the ureteric bud as an outgrowth of the wolffian duct is induced by signalling molecules (such as GDNF) that emanate from the adjacent metanephrogenic mesenchyme. Once it has invaded the mesenchyme, growth and branching of the bud is controlled by a variety of molecules, such as the growth factors GDNF, HGF, TGFbeta, activin, BMP-2,
BMP-7
, and matrix molecules such as heparan sulphate proteoglycans and laminins. These various influences are integrated by signal transduction systems inside ureteric bud cells, with the MAP kinase, protein kinase A and protein kinase C pathways appearing to play major roles. The mechanisms of morphogenetic change that produce branching remain largely obscure, but matrix metalloproteinases are known to be necessary for the process, and there is preliminary evidence for the involvement of the actin/myosin contractile cytoskeleton in creating branch points.
...
PMID:Intracellular and extracellular regulation of ureteric bud morphogenesis. 1132 19
