Activin RIB/ALK-4 Protein, Human (HEK293, His)

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, His) is produced in HEK293 cells with six C-Terminal His-tags. It consists of 103 amino acids (S24-E126).

ALK4, also termed activin A receptor type 1b (ACVR1B), is a transmembrane serine/threonine kinase activin type-I receptor and is highly expressed in the mammal heart. ALK4 is an important regulator of vertebrate development, with roles in mesoderm induction, primitive streak formation, gastrulation, dorsoanterior patterning, and left-right axis determination^[1][2].
The sequence of amino acids in ALK4 (ACVR1B) proteins from different species is very stable, which leads to the conclusion that in the process of evolution, ALK4 has been only slightly altered, and that both in humans and in animals, its function is similar.
Activin binds to a type II activin receptor (Acvr2 or Acvr2b) and then recruits ACVR1B. ALK4 (ACVR1B) forms an activin receptor complex with activin type-II receptor to transduce activin signal from the cell surface to the cytoplasm, thus regulating physiological and pathological processes including embryogenesis, tissue homeostasis, wound healing, extracellular matrix production, immunosuppression, and carcinogenesis. Receptor heterodimerization activates the type II receptor kinase to phosphorylate the type I receptor, which recruits and phosphorylates regulated Smads2 and 3. Phosphorylated regulated Smads are released and form a heteromeric complex with the Co-Smad, Smad4. The regulated Smad and Co-Smad complex then translocates to the nucleus where it regulates the expression of many genes. In mammals, Acvr1b is expressed by various types of epithelial cells, including interfollicular epidermis, and the outer root sheath (ORS) and the inner root sheath (IRS) of the hair follicles. Activin signaling through Acvr1b acts on skin epithelial cells in a paracrine manner^[1][2][3].
ALK4 (ACVR1B), is an important regulator of vertebrate development, with roles in mesoderm induction, primitive streak formation, gastrulation, dorsoanterior patterning, and left-right axis determination. ALK4 also regulates physiological and pathological processes including embryogenesis, tissue homeostasis, wound healing, extracellular matrix production, immunosuppression, and carcinogenesis. ALK4 functions as a tumor-suppressor gene in pancreatic tumorigenesis^[1][2][3][4].

Recombinant ALK4 (25-500 ng) and recombinant PTP1B together at 30°C resultes in the apparent cleavage of PTP1B. PTP1B is cleaved after 30 min of Activin treatment, suggesting that Activin causes an interaction between ALK4 and PTP1B that leads to the cleavage of PTP1B by ALK4^[5].

This product does not contain protein kinase domain.

Human

HEK293

C-6*His

P36896 (S24-E126)

91  [NCBI]

Extracellular Domain

SGPRGVQALLCACTSCLQANYTCETDGACMVSIFNLDGMEHHVRTCIPKVELVPAGKPFYCLSSEDLRNTHCCYTDYCNRIDLRVPSGHLKEPEHPSMWGPVE

Approximately 14-20 kDa, based on SDS-PAGE under reducing conditions, due to the glycosylation.

• 
  ≥ 90%, as determined by reducing SDS-PAGE.

Lyophilized powder.

Lyophilized from a 0.22 μm filtered solution of 20 mM PB, 150 mM NaCl, pH 7.4.

<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 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]. 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]