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http://hedgehog.sfsu.edu/transduct_mod.html
In the absence of Hh, Patched (ptc) prevents Smoothened (smo) from activating down stream components. Ptc is a 12 transmembrane spanning protein with a sterol sensing domain (Hooper and Scott, 1989; Lum and Beachy, 2004). Smo is a 7 transmembrane spanning protein with homology to G-protein coupled receptors (Alcedo et. al.1996; Lum and Beachy, 2004). It has not been determined mechanisticly how Ptc prevents Smo from activating the Hh pathway. A complex of several key cytoplasmic effectors has been noted. These include: Costal-2 (cos2) a kinesin-related microtubule binding protein (Robbins et al., 1997; Sisson et al., 1997; Lum et al. 2003; Zhang et al., 2005), Fused (Fu), a putative serine/threonine kinase (Therond et al., 1996), Supressor of fused (Sufu), a scafold protein (Pham et. al., 1995; Chen et al., 1999) and a transcription factor Cubitus interruptus (Ci) (Aza-Blanc et al., 1997; Chen et al., 1999).Minimal phosphorylation of both Fu and Cos2 in the absence of Hh has been noted (Ogden et. al.,2004).
Full length Ci 155 is phosphorylated by various kinases (Caesin kinase I (Ck1), Glycogen syntase kinase 3 (GSK3), and Protein kinase A (PKA) (Price and Kalderon, 2002; Zhang et al., 2005). Phosphorylation of Ci leads to cleavage and ubiquitination (Price and Kalderon, 2002; Zhang et al., 2005).
Ci75, a truncated form of Ci, moves into the nucleus and functions as a repressor (Aza-Blanc et al., 1997; Chen et al., 1999)
Hedgehog Activation
Upon Hh reception, inhibition of smo by ptc is released by some unknown mechanism leading to activation of the pathway (Lum and Beachy,2004).
Smo has been shown to be phosphoryated by G-protein coupled receptor kinase 2 (Grk2) (Chen et. al., 2004; Ogden et. al.,2004).
A phosphorylated form of Smo attracts beta Arrestin 2 (bArrb2) and the formation of a clathrin coated pit for internalization (Chen et. al., 2004). Cos2 associates with phosphorylated smo. Cos2 forms a scafold on which a complex of Fu, Ci, and Sufu (Lum et al., 2003) associates. Reception of Hh also converts Fu to a hyperphosphorylated form, (Therond et al.,1996; Ramirez-Weber et al., 2000; Stegman et al. 2001) leading to inhibition of Ci proteolysis (Aza- Blanc et al., 1997; Price and Kalderon, 2002; Zhang et al., 2005).
have been shown to be assocatiated with Smo, Cos2, Fu, Ci, and SuFu in mammalian cilia (Corbit et al., 2005; Huangfu et al., 2003; Huangfu and Anderson, 2005; Liu et al, 2005).
