SHH, Human, HEK293 Cells,Tag Free

Sonic Hedgehog (Shh) is expressed in embryonic tissues that are critical for the patterning of the developing central nervous system, somite, and limb. It is also involved in whisker, hair, foregut, tooth, and bone development. Shh regulates neural and hematopoietic stem cell fate and is important for  thymocyte differentiation and proliferation as well as T cell determination. In adult tissue Shh is associated with cancer development and tissue remodeling  following injury (1-3). Human Shh encodes a 462 amino acid (aa) precursor protein that is autocatalytically processed to yield a non-glycosylated 19 kDa  N-terminal fragment (Shh-N) and a glycosylated 25 kDa C-terminal protein (Shh-C) (4). Shh-C, which is responsible for the intramolecular processing  of Shh, is rapidly degraded following Shh proteolysis (5). Shh-N is highly conserved, sharing >98% aa identity between mouse, human, rat, canine, porcine, and chicken Shh-N. Shh-N can be palmitoylated at its N-terminal cysteine and modified by cholesterol addition at its C-terminus (6). These  modifications contribute to the membrane tethering of Shh as well as its assembly into various sized multimers (6-9). Lipid modification and  multimerization greatly increase Shh-N receptor binding affinity and signaling potency (5, 6, 8, 9). Monomeric and multimeric Shh can be released from  the plasma membrane by the cooperative action of DISP1, SCUBE2, and TACE/ADAM17 (10-12). Modifications also extend the effective range of Shh  functionality and are required for the development of protein gradients important in tissue morphogenesis (9, 13). Canonical signaling of Shh is mediated  by a multicomponent receptor complex that includes Patched (PTCH1, PTCH2) and Smoothened (SMO) (14)

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4. Marigo, V. et al. (1995) Genomics 28:44. 

5. Zeng, X. et al. (2001) Nature 411:716. 

6. Feng, J. et al. (2004) Development 131:4357. 

7. Goetz, J.A. et al. (2006) J. Biol. Chem. 281:4087. 

8. Pepinsky, R.B. et al. (1998) J. Biol. Chem. 273:14037. 

9. Pepinsky, R.B. et al. (1998) J. Biol. Chem. 273:14037. 

10. Chen, M.-H. et al. (2004) Genes Dev. 18:641. 

11. Etheridge, L.A. et al. (2010) Development 137:133. 

12. Jakobs, P. et al. (2014) J. Cell Sci. 127:1726. 

13. Dierker, T. et al. (2009) J. Biol. Chem. 284:8013. 

14. Lewis, P.M. et al. (2001) Cell 105:599