The TGF-beta superfamily comprises several different extracellular factors. The factors bind to and activate the membrane-bound TGF-beta receptor, which is a serine-threonine kinase. Autophosphorylated and thereby activated TGF-beta receptor activates Smad proteins, which transmit the...
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The JAK/STAT pathway begins with the activation of a membrane bound cytokine receptor by interferon or another cytokine. The activated receptor recruits and activates intracellular tyrosine kinases of the JAK family. Active JAKs phosphorylate STAT proteins, which then dimerize, enter the...
In normal cells, activation of the hedgehog signaling pathway begins with the binding of the extracellular hedgehog protein to the membrane receptor Patched. The activation of Patched overcomes the blockage of the membrane receptor Smoothened. Active Smoothened is able to activate Gli2...
Onkoview 2015
The hedgehog signaling pathway – Part 2: Activation of the Hedgehog pathway in basal cell carcinoma and medulloblastoma
The hedgehog signaling pathway is constitutively active in cells of basal cell carcinoma and medulloblastoma. This activation is caused by the mutational inactivation or the deletion of the Patched-coding gene PTCH or by activating mutations in the gene SMO, which codes for Smoothened...
Onkoview 2015
The hedgehog signaling pathway – Part 3: Inhibition of the Hedgehog pathway by drugs binding to Smoothened
Tumor cells with constitutively active hedgehog signaling pathway can be treated with drugs that bind directly to and inhibit Smoothened. Unfortunately, the effect of these drugs does not last longer than 6 months before the tumor cells develop resistance. The responsible mechanisms...
