Hedgehog signaling pathway
The Hedgehog signaling pathway is a crucial cell-cell communication mechanism in developmental processes, affecting cell proliferation, differentiation, and tissue morphogenesis.
Hedgehog Family Ligands: Hedgehog is a class of secreted signaling proteins, including Sonic Hedgehog (Shh), Indian Hedgehog (Ihh), and Desert Hedgehog (Dhh).
Receptors: Hedgehog signals are transmitted by binding to two receptors on the cell surface, Patched (Ptch) and Smoothened (Smo).
Function of Ptch and Smo: In the absence of the Hh ligand, Ptch inhibits the activity of Smo. When the Hh ligand binds to Ptch, the inhibitory effect of Ptch is lifted, leading to the activation of Smo.
Signal Transduction: The activation of Smo triggers a series of downstream signaling events, including the activation of Gli family transcription factors.
Transcription Factor Activation: In mammals, there are three Gli transcription factors (Gli1, Gli2, Gli3), which play different roles in the signaling pathway. The activation of Smo leads to Gli transcription factors entering the cell nucleus and activating the transcription of Hedgehog target genes.
Target Gene Expression: The activation of the Hedgehog signaling pathway leads to the expression of a series of target genes involved in cell proliferation, differentiation, and tissue morphogenesis.
Signal Regulation: The activity of the Hedgehog signaling pathway is regulated by various mechanisms, including self-inhibition of receptors, phosphorylation by protein kinases, and protein degradation.
Biological Functions: The Hedgehog signaling pathway plays an important role in embryonic development, tissue regeneration, and stem cell maintenance.
Disease Association: Abnormal activation of the Hedgehog signaling pathway is associated with various diseases, especially cancer, such as basal cell carcinoma, medulloblastoma, and certain types of lung cancer.
Therapeutic Potential: Due to its role in disease development, the Hedgehog signaling pathway has become an important target for drug development, particularly in the field of cancer therapy.
Drug Targets
