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Patched

Patched. www.orlandoskindoc.com/ basal_cell_carcinoma.htm. The Basics-Core Players In Hedgehog signaling. PTCH codes for a 12 pass transmembrane receptor. It binds to a ligand known as Sonic hedgehog (Shh).

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Patched

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  1. Patched www.orlandoskindoc.com/ basal_cell_carcinoma.htm

  2. The Basics-Core Players In Hedgehog signaling • PTCH codes for a 12 pass transmembrane receptor • It binds to a ligand known as Sonic hedgehog (Shh) • Normally functions to inhibit Smoothened (Smo), a constitutively active G-protein coupled receptor Wetmore, C. Current Opinion in Genetics and Development 2003, 13:34-42.

  3. Fu SUFU Cos2 What else is downstream? • Microtubule • And ULTIMATELY • the transcription factor Gli Wetmore C. Current Opinion in Genetics and Development 2003, 13:34-42.

  4. PTCH Signaling Pathway Absence of Shh Ligand Gilbert, S.F. Developmental Biology , 6th Ed.

  5. PTCH Signaling Pathway Presence of Shh Ligand Gilbert, S.F. Developmental Biology , 6th Ed.

  6. What is this Signaling Pathway Used for? Make Mice homozygous Patched mutant and observe… Defects in neural tube closure! Normal Ptc -/- Goodrich, L.V. et al. Science 1997, 277:1109-1113.

  7. What is this Signaling Pathway Used for? Make Mice heterozygous mutant for Patched and observe… Medulloblastomas! Normal Ptc -/+ Wetmore C. Current Opinion in Genetics and Development 2003, 13:34-42.

  8. Patched is a target gene of the pathway and acts as a feedback negative regulator Patched is expressed in hair follicles of developing mice Wicking C, Smyth I and Bale A. Oncogene 1999, 18:7844-7851.

  9. How does this Relate to Cancer? In basal cell carcinoma one finds… • Mutations that Activate • Mutations that Inactivate Reviewed in Wicking C, Smyth I and Bale A. Oncogene 1999, 18:7844-7851.

  10. Applying the Brakes • Cyclopia Gilbert, S.F. Developmental Biology , 4th Ed.

  11. Applying the Brakes Veratum californicum Incardona, JP et al. Development 1998, 125:3553-3562

  12. Applying the Brakes Motor Neurons (Red) Floor Plate Cells (Green) Incardona, JP et al. Development 1998, 125:3553-3562

  13. Applying the Brakes Berman et al. Nature 2003, 425:846-851.

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