SMAD4 蛋白, Human (His)

SMAD4 is a class of common mediator SMAD (Co-SMAD), which belongs to the dwarfin/SMAD family. It conducts cell signals through the SMAD4/TGF-β pathway and plays an important role in promoting bone development and tissue homeostasis. SMAD4 induces chondrogenesis of human bone marrow mesenchymal stem cells, and specifically targets stem cells to participate in self-renewal of hematopoietic stem cells. SMAD4 can also protect cell apoptosis and inhibit epithelial cell proliferation, showing antitumor effects^[1][2]. SMAD4 Protein, Human (His) has the 552 a.a. sequence (M1-D552), produced in E.coli with C-terminal 6*His-tag.

SMAD4 属于 dwarfin/SMAD 家族。SMAD 是一组将细胞外信号直接传递至细胞核的蛋白质。哺乳动物SMAD可分为三类：受体调节型SMAD（R-SMAD）、共同介导型SMAD（Co-SMAD）和抑制型SMAD（I-SMAD）。(1)R-SMAD包括SMAD1、SMAD2、SMAD3、SMAD5和SMAD8/9，其中Smad2/3介导TGF-β亚家族成员的信号转导。SMAD1/5/8 介导骨形态发生蛋白 (BMP) 亚家族成员的信号传导。(2) Co-SMAD包括SMAD4，它是TGF-β和BMP信号通路的中心介质。(3) I-SMAD，包括SMAD6和SMAD7，抑制R-SMAD受体介导的磷酸化，从而阻止与Co SMAD形成复合物。SMAD4 在骨发育（从软骨细胞前体到成熟骨细胞）和组织稳态的细胞信号传导中发挥重要作用。具体而言，TGF-β向上游发出信号，激活SMAD4和R-SMAD（即SMAD2/3）相互作用并形成调节靶基因表达的寡聚物复合物。然而，SMAD3/4主要诱导人骨髓间充质干细胞的软骨形成。SMAD4的异常表达可以抑制动物模型中的软骨生成，甚至导致细胞生长失控和肿瘤诱导。SMAD4 还专门针对干细胞，可能参与造血干细胞的自我更新。同时，SMAD4调节软骨细胞的细胞极性，影响软骨细胞的形状、大小、迁移和方向。它还通过SMAD4/TGF-β途径促进不同细胞中的细胞迁移、粘附和细胞骨架组织生成。SMAD4/TGF-β通路还受到MAPK、PI3K/AKT和WNT/β-catenin等经典通路的广泛调控，形成复杂的网络。SMAD4 还调节细胞凋亡，通过抑制颗粒细胞凋亡导致滤泡闭锁。在结直肠癌细胞中，TGF-β 诱导 Smad4 依赖性上皮间质转化，从而导致细胞凋亡。SMAD4对细胞凋亡的保护作用也是软骨细胞分化和增殖的关键。此外，细胞凋亡对于分化和骨稳态至关重要，即成骨细胞凋亡促进破骨细胞生成和骨吸收，这是骨稳态的重要过程。SMAD4 还控制早期肢芽中的基因调控网络，软骨细胞特异性 Smad4-KO 小鼠表现出侏儒症和生长板组织受损。SMAD4 蛋白还抑制上皮细胞增殖、减少血管生成和增加血管通透性，表现出抗肿瘤作用^[1][2]。

SMAD4 敲除，会抑制 TGFβ/激活素/淋巴结受体信号传导，而使人类胚胎干细胞 (hESCs) 的快速分化受到限制^[3]。

Human

E. coli

C-6*His

Q13485 (M1-D552)

4089  [NCBI]

MDNMSITNTPTSNDACLSIVHSLMCHRQGGESETFAKRAIESLVKKLKEKKDELDSLITAITTNGAHPSKCVTIQRTLDGRLQVAGRKGFPHVIYARLWRWPDLHKNELKHVKYCQYAFDLKCDSVCVNPYHYERVVSPGIDLSGLTLQSNAPSSMMVKDEYVHDFEGQPSLSTEGHSIQTIQHPPSNRASTETYSTPALLAPSESNATSTANFPNIPVASTSQPASILGGSHSEGLLQIASGPQPGQQQNGFTGQPATYHHNSTTTWTGSRTAPYTPNLPHHQNGHLQHHPPMPPHPGHYWPVHNELAFQPPISNHPAPEYWCSIAYFEMDVQVGETFKVPSSCPIVTVDGYVDPSGGDRFCLGQLSNVHRTEAIERARLHIGKGVQLECKGEGDVWVRCLSDHAVFVQSYYLDREAGRAPGDAVHKIYPSAYIKVFDLRQCHRQMQQQAATAQAAAAAQAAAVAGNIPGPGSVGGIAPAISLSAAAGIGVDDLRRLCILRMSFVKGWGPDYPRQSIKETPCWIEIHLHRALQLLDEVLHTMPIADPQPLD

Approximately 62.0-68.0 kDa

Greater than 80% as determined by reducing SDS-PAGE.

无菌粉末.

Lyophilized from a 0.2 μm filtered solution of 20 mM Tris-HCl, pH 8.0.

<1 EU/μg, determined by LAL method.

It is not recommended to reconstitute to a concentration less than 100 μg/mL in ddH₂O. For long term storage it is recommended to add a carrier protein (0.1% BSA, 5% HSA, 10% FBS or 5% Trehalose).

Stored at -20°C for 2 years. 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]. Pakravan K, et al. SMAD4 contributes to chondrocyte and osteocyte development. J Cell Mol Med. 2022 Jan;26(1):1-15.  [Content Brief]

  [2]. Zhao M, et al. The role of TGF-β/SMAD4 signaling in cancer. Int J Biol Sci. 2018 Jan 12;14(2):111-123.  [Content Brief]

  [3]. Avery S, et al. The role of SMAD4 in human embryonic stem cell self-renewal and stem cell fate. Stem Cells. 2010 May;28(5):863-73.  [Content Brief]