Activin RIB/ALK-4 蛋白, Human (HEK293, Fc)

Activin RIB, also known as activin receptor type-1B (ACVR1B) or ALK-4, is a type I transmembrane serine/threonine kinase receptor that is part of the TGF-β receptor superfamily. Activin binds to a type II activin receptor (ACVR2or ACVR2B) and then recruits ACVR1B^[1][2][3]. Activin RIB/ALK-4 Protein, Human (HEK293, Fc) is produced in HEK293 cells with a C-Terminal Fc-tag. It consists of 126 amino acids (M1-E126).

ALK4 也称为激活素 A 受体 1b 型 (ACVR1B)，是一种跨膜丝氨酸/苏氨酸激酶激活素 I 型受体，在哺乳动物心脏中高度表达。ALK4 是脊椎动物发育的重要调节因子，在中胚层诱导、原条形成、原肠胚形成、背前部模式形成和左右轴确定中发挥作用^[1][2]。
不同物种的ALK4（ACVR1B）蛋白的氨基酸序列非常稳定，由此得出的结论是，在进化过程中，ALK4仅发生了轻微的改变，无论在人类还是动物中，其功能类似。
激活素与 II 型激活素受体（Acvr2 或 Acvr2b）结合，然后招募 ACVR1B。ALK4（ACVR1B）与激活素II型受体形成激活素受体复合物，将激活素信号从细胞表面转导至细胞质，从而调节胚胎发生、组织稳态、伤口愈合、细胞外基质产生、免疫抑制和癌变等生理和病理过程。受体异二聚化激活 II 型受体激酶，使 I 型受体磷酸化，从而募集并磷酸化受调节的 Smad2 和 3。磷酸化的受调节 Smad 被释放，并与 Co-Smad、Smad4 形成异聚复合物。然后，受调节的 Smad 和 Co-Smad 复合物易位到细胞核，在那里调节许多基因的表达。在哺乳动物中，Acvr1b 由多种类型的上皮细胞表达，包括毛囊间表皮、毛囊的外根鞘 (ORS) 和内根鞘 (IRS)。激活素信号通过 Acvr1b 以旁分泌方式作用于皮肤上皮细胞^[1][2][3]。
ALK4 ( ACVR1B) 是脊椎动物发育的重要调节因子，在中胚层诱导、原条形成、原肠胚形成、背前模式和左右轴确定中发挥作用。ALK4 还调节生理和病理过程，包括胚胎发生、组织稳态、伤口愈合、细胞外基质产生、免疫抑制和癌发生。ALK4 在胰腺肿瘤发生中充当肿瘤抑制基因^[1][2][3][4]。

Recombinant ALK4 (25-5 ng) and recombinant PTP1B together at 3°C resultes in the apparent cleavage of PTP1B. PTP1B is cleaved after 3 min of Activin treatment, suggesting that Activin causes an interaction between ALK4 and PTP1B that leads to the cleavage of PTP1B by ALK4^[5].

Human

HEK293

C-hFc

P36896 (S24-E126)

91  [NCBI]

Approximately 38.1 kDa

Greater than 90% as determined by reducing SDS-PAGE.

<1 EU/μg, determined by LAL method.

• [1]. Dev Dyn, et al. Developmental analysis of activin-like kinase receptor-4 (ALK4) expression in Xenopus laevis. . 2005 Feb;232(2):393-8.  [Content Brief]

  [2]. Qian Wang, et al. Activin Receptor-Like Kinase 4 Haplodeficiency Mitigates Arrhythmogenic Atrial Remodeling and Vulnerability to Atrial Fibrillation in Cardiac Pathological Hypertrophy. J Am Heart Assoc. 2018 Aug 21;7(16):e008842.  [Content Brief]

  [3]. Wanglong Qiu, et al. Conditional activin receptor type 1B (Acvr1b) knockout mice reveal hair loss abnormality. J Invest Dermatol. 2011 May;131(5):1067-76.  [Content Brief]

  [4]. G H Su, et al. ACVR1B (ALK4, activin receptor type 1B) gene mutations in pancreatic carcinoma. Proc Natl Acad Sci U S A. 2001 Mar 13;98(6):3254-7.  [Content Brief]

  [5]. Kamil Matulka, et al. PTP1B is an effector of activin signaling and regulates neural specification of embryonic stem cells. Cell Stem Cell. 2013 Dec 5;13(6):706-19.  [Content Brief]