Smoothened Receptor Antibodies

Smoothened (SMO) is a non-classical 7TM receptor that is a central part of the hedgehog signaling system, which is of eminent importance for proper embryogenesis and tumorigenesis. The secreted lipoglycoproteins of the hedgehog family (sonic, Indian and desert hedgehog) bind the transmembrane protein patched (PTCH1, PTCH2), which constitutively inhibits SMO. Upon hedgehog binding to PTCH, this inhibition is released, resulting in the activation of SMO and initiation of SMO-downstream signaling. SMO exerts its effects by activating heterotrimeric G proteins or stabilization of GLI by sequestering catalytic PKA subunits. SMO communicates with GLI transcription factors by directly binding the PKA catalytic subunit and physically blocking its enzymatic activity. In fact, GPCR kinase 2 (GRK2) regulates this process during endogenous Hh signal transduction in the vertebrate primary cilium. Hh pathway activation triggers rapid GRK2 relocalization from the base to the shaft of the cilium, leading to SMO phosphorylation of carboxyl-terminal serine594/threonine597serine599 (pS594/pT597/pS599-SMO). This nomenclature refers to the mouse SMO receptor. This phosphorylation motif is highly conserved across species. It is identical in rats and corresponds to serine590/threonine593/serine595 (pS590/pT593/pS595-SMO) in humans. For more information on SMO receptor pharmacology please refer to the IUPHAR database. For further reading refer to:

Schulte G. International Union of Basic and Clinical Pharmacology. LXXX. The class Frizzled receptors. Pharmacol Rev. 2010 Dec;62(4):632-67. doi: 10.1124/pr.110.002931. PMID: 21079039.

Walker MF, Zhang J, Steiner W, Ku PI, Zhu JF, Michaelson Z, Yen YC, Long AB, Casey MJ, Poddar A, Nelson IB, Arveseth CD, Nagel F, Clough R, LaPotin S, Kwan KM, Schulz S, Stewart RA, Tesmer JJG, Caspary T, Subramanian R, Ge X, Myers BR. A Ciliary SMOOTHENED-GRK2-PKA Signaling Pathway Initiates Hedgehog Signal Transduction. bioRxiv. 2023 May 11:2023.05.10.540226. doi: 10.1101/2023.05.10.540226. PMID: 37214942; PMCID: PMC10197709.