The study of posttranslational regulation of proteins has occupied biochemists for well over a half century. Understanding balanced phosphorylation and dephosphorylation of the proteins may be the key to meeting some of the most pressing scientific challenges. A detailed examination of the phosphorylation of many components in the Hedgehog (Hh) pathway leads to a better understanding of the Hh signaling mechanisms. This chapter describes the precise phosphorylation that evolves during the phosphorylation/dephosphorylation of players in the Hh signaling cascade, including the signal transducer Smoothened and the transcription factor Ci/Gli.
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