GDF-15 蛋白, Mouse (HEK293, Fc)

Growth differentiation factor 15 (GDF-15) is a polypeptide hormone belonging to the transforming growth factor β (TGF-β) superfamily. GDF-15 is also known as non-steroidal anti-inflammatory drug activating Gene-1 (NAG-1), placental transforming growth factor-β (PTGFB), prostate-derived factor (PDF), and placental bone morphogenetic protein (PLAB). GDF-15 binds to glial cell-derived neurotrophic factor (GDNF) family receptor alpha-like protein (GFRAL) and is involved in aging, cancer, and metabolic processes. GFRAL-GDF15 does not affect SMAD activity and activates intracellular signals including RET, AKT, ERK1/2, and phospholipase C (PLCγ)^[1]. GDF-15 Protein, Mouse (HEK293, Fc) has 115 amino acids expressed by HEK293 cells with N-terminal hFc tag.

生长分化因子 15 (GDF-15) 是一种多肽激素，属于转化生长因子 β (TGF-β) 超家族。GDF-15 在胎盘中高表达，在前列腺和结肠中低表达，在肾脏中也有一定程度的表达。因此GDF-15又称为胎盘转化生长因子PGF-β、胎盘骨形态发生蛋白PLAB、前列腺衍生因子PDF。GDF-15在生理学和病理学方面具有广泛的生物学功能，特别是在衰老、癌症和代谢过程中。GDF-15 最初储存在细胞外基质 (ECM) 中，在外部刺激下进行蛋白水解，形成活性形式，并快速分泌到循环中。在小鼠心肌细胞中，GDF-15 的裂解过程可能由 PCSK 家族的酶催化，形成成熟的二聚体形式。GDF15启动子位点的上游有多种转录因子的结合位点，包括特异性蛋白1（Sp1）、早期生长反应蛋白1（Egr-1）、p53和COUP转录因子1（COUP-TF1）。GDF-15的受体是α样蛋白(GFRAL)，是胶质细胞源性神经营养因子(GDNF)家族的受体。GFRAL-GDF15 复合物与酪氨酸激酶辅助受体 RET 结合，导致 RET 磷酸化。随后，GFRAL-GDF15 继续激活 AKT、ERK1/2 和磷脂酶 C (PLCγ) 的细胞内信号通路，但不激活 SMAD 通路。GDF-15 在组织损伤和炎症等许多病理状态期间和之后过度表达。促成这一结果的刺激因素包括氧化低密度脂蛋白 (oxLDL)、细胞因子和生长因子，如 IL-1β、TNF-α、血管紧张素 II、巨噬细胞集落刺激因子 M-CSF 和 TGFβ。GDF-15又称NSAIDS药物激活基因NAG-1，可能通过抑制巨噬细胞激活而发挥抗炎作用。GDF-15 还抑制 NFκB 的活性或多种细胞因子的表达，包括干扰素 (IFN-γ)、白介素-6 (IL-6)、单核细胞趋化蛋白-1 (MCP-1) 和肿瘤坏死因子-α （肿瘤坏死因子-α）。GDF-15对急性肾损伤（AKI）和心肌功能障碍引起的内毒素诱导的脓毒症具有显着的抵抗力。GDF-15 似乎还能促进恶性肿瘤晚期的肿瘤生长。据报道，血清 GDF15 水平升高是癌症进展的潜在生物标志物，包括乳腺癌、结肠癌、胰腺癌和前列腺癌等。在人和食蟹猴中，GDF-15蛋白的氨基酸序列相似性较高，相似率为91.56%。与小鼠和大鼠的氨基酸序列相比，人GDF-15的相似性较低（分别为59.73%和59.39%）^[1]。

GDF-15 敲除小鼠表现出较小的基于铂的治疗诱导的厌食症和体重减轻，而用单克隆抗体mAB1中和GDF-15可提高生存率^[2]。

Immobilized Mouse GFRAL-His at 2 μg/mL (100μL/well) on the plate. Dose response curve for Mouse GDF15-hFc with the EC₅₀ ≤ 6.5 ng/mL determined by ELISA.

Mouse

HEK293

N-hFc

Q9Z0J7 (S189-A303)

23886  [NCBI]

40-50 kDa

Greater than 95% as determined by Tris-Bis PAGE.

无菌粉末.

Lyophilized from a 0.22 μm filtered solution of PBS, pH 7.4. Normally 5% trehalose is added as protectant 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. 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]. Assadi A, et al. GDF15, an update of the physiological and pathological roles it plays: a review. Pflugers Arch. 2020 Nov;472(11):1535-1546.  [Content Brief]

  [2]. Breen DM, et al. GDF-15 Neutralization Alleviates Platinum-Based Chemotherapy-Induced Emesis, Anorexia, and Weight Loss in Mice and Nonhuman Primates. Cell Metab. 2020 Dec 1;32(6):938-950.e6.  [Content Brief]