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Hedgehog Signaling
Author(s) -
WASCHEK JAMES A.,
DICICCOBLOOM EMANUEL,
NICOT ARNAUD,
LELIEVRE VINCENT
Publication year - 2006
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1317.089
Subject(s) - g protein coupled receptor , sonic hedgehog , biology , microbiology and biotechnology , hedgehog signaling pathway , hedgehog , signal transduction , smoothened , adenylyl cyclase , patched , protein kinase a , kinase
Hedgehog (HH) is a secreted protein named for the bristle phenotype observed in Drosophila embryos that lack the corresponding gene. Three homologs have been characterized in vertebrates, all which have critical roles in the development of multiple organ systems. Moreover, these proteins regulate stem cell production and activation during tissue repair after injury, and appear to drive proliferation in a variety of type of tumors, including those arising in the brain, foregut, lung, breast, pancreas, stomach, and prostate. Early evidence from Drosophila , and later work in vertebrates established the cAMP/protein kinase A (PKA) pathway as a major pathway which opposes HH signaling, doing so by phosphorylating intracellular signaling mediators and targeting them for degradation. Thus, it seems possible that ligands which activate G protein–coupled receptors (GPCR) may act in some cases to oppose or enhance HH signaling. We studied a possible interaction of pituitary adenylyl cyclase‐activating peptide (PACAP) with sonic hedgehog (SHH) in the developing cerebellum, where both PACAP and SHH are know to act. PACAP and the PAC1‐specific agonist, maxadilan, were found to completely block the proliferative action of SHH on developing cerebellar granule neurons. It remains to be determined if HH/GPCR antagonistic interactions play additional important roles in development, plasticity, tissue repair, cancer, and other processes.