SHH Protein, Human (HEK293, His)

Sonic Hedgehog (SHH) Protein is a secretory glycoprotein of the Hedgehog family that can self-cleave to form N-SHH. SHH Protein activates Smo by binding to Frizzled and LRP6, inhibits GSK-3β to stabilize β-catenin, and activates FOXM1. SHH Protein also promotes NO release and shortens myocardial APD by phosphorylating eNOS through PI3K/Akt. SHH Protein can promote the maturation of sweat gland cells in three-dimensional culture and play a cardioprotective role in the pig ischemia-reperfusion model^[1][2]. SHH Protein, Human (HEK293, His) is a recombinant human SHH protein expressed in HEK293 cells with C-terminal His-tag.

Sonic Hedgehog (SHH) Protein is a secreted glycoprotein of the Hedgehog family whose transcription is regulated by a long-range regulatory mechanism involving multiple enhancers. The N-terminus of SHH Protein contains a cysteine-rich domain with glycosylation sites and a cholesterol-binding domain at the C-terminus, which can form an N-terminal active fragment (N-SHH) by self-cleavage. In the endoplasmic reticulum, ShhC is degraded, leaving behind the lipidated ShhNp that is essential for developmental patterning. SHH Protein is extensively modified by cleavage and post-translational modifications, and its release from producer cells can also be regulated by interactions with Dispatched, Scube2, and heparan sulfate proteoglycans.
SHH signaling is involved in embryonic development (including lung) and patterning during development. As a ligand of the classic Hedgehog signaling pathway, SHH Protein binds to the transmembrane receptor Frizzled (such as Frizzled-1) and the co-receptor LRP6, activates Smoothened (Smo) and inhibits GSK-3β, relieves β-catenin degradation and causes its nuclear translocation, and activates anti-apoptotic genes such as FOXM1. At the same time, SHH Protein can promote NO release by phosphorylating eNOS through the PI3K/Akt pathway and shorten the action potential duration (APD) of cardiomyocytes. The biological activities of SHH Protein include promoting the maturation of sweat gland cells in three-dimensional culture (upregulating markers such as CK19) and myocardial protection in the pig ischemia-reperfusion model (reducing infarct volume and inhibiting arrhythmias). It is mainly used in the research of tissue engineering (sweat gland regeneration), ischemic diseases (such as myocardial infarction), prostate cancer and other diseases^{[1][2][3][4][5]}.

Measured by its ability to induce alkaline phosphatase production by C3H10T1/2 mouse embryonic fibroblast cells and the ED₅₀ is typically 1-10 μg/mL.

Human

HEK293

C-His

Q15465 (M1-G197)

6469  [NCBI]

Partial

MLLLARCLLLVLVSSLLVCSGLACGPGRGFGKRRHPKKLTPLAYKQFIPNVAEKTLGASGRYEGKISRNSERFKELTPNYNPDIIFKDEENTGADRLMTQRCKDKLNALAISVMNQWPGVKLRVTEGWDEDGHHSEESLHYEGRAVDITTSDRDRSKYGMLARLAVEAGFDWVYYESKAHIHCSVKAENSVAAKSGG

Approximately 24 kDa, based on SDS-PAGE under reducing conditions, due to the glycosylation.

≥ 95%, as determined by reducing SDS-PAGE.

Lyophilized powder.

Lyophilized from a 0.2 μm filtered solution of PBS, pH 7.4. Normally 5 % - 8 % trehalose, mannitol and 0.01% Tween 80 are added as protectants before lyophilization.

<1 EU/μg, determined by LAL method.

It is not recommended to reconstitute to a concentration less than 100 μg/mL in ddH₂O.

Stored at -20°C for 2 years from date of receipt. After reconstitution, it is stable at 4°C for 1 week or -20°C for longer (with carrier protein). It is recommended to freeze aliquots at -20°C or -80°C for extended storage.

Room temperature in continental US; may vary elsewhere.

• [1]. Wang XZ, et al. Sonic hedgehog (Shh) and CC chemokine ligand 2 signaling pathways in asthma. J Chin Med Assoc. 2019;82(5):343-350.  [Content Brief]

  [2]. Seo H, et al. Upstream Enhancer Elements of Shh Regulate Oral and Dental Patterning. J Dent Res. 2018;97(9):1055-1063.  [Content Brief]

  [3]. Huang Z, et al. Shh promotes sweat gland cell maturation in three-dimensional culture. Cell Tissue Bank. 2016 Jun;17(2):317-25.  [Content Brief]

  [4]. Ghaleh B, et al. Cardioprotective effect of sonic hedgehog ligand in pig models of ischemia reperfusion. Theranostics. 2020 Mar 4;10(9):4006-4016.  [Content Brief]

  [5]. Spinella-Jaegle S, et al. Sonic hedgehog increases the commitment of pluripotent mesenchymal cells into the osteoblastic lineage and abolishes adipocytic differentiation. J Cell Sci. 2001 Jun;114(Pt 11):2085-94.  [Content Brief]