Activin A Protein, Human/Mouse/Rat (HEK293)

Activin A, a multifunctional cytokine, is a member of TGF-β superfamily. Activin A first binds to the type II activin receptors (ActIIRA or ActRIIB) on the member surface, and then recruits and phosphorylates type I activin receptors (ActRI). Activin A primarily signal through SMAD2/3 proteins to regulate a variety of functions, including inflammation, fibrosis, and tumorigenesis^[1]. Activin A Protein, Human/Mouse/Rat (HEK293) is produced in HEK293 cells, and consists of 117 amino acids (G310-S426).

Activin is a member of transforming growth factor-β (TGF-β) superfamily consisting of two inhibin β subunits linked by disulfide bonds. Activin A is expressed widely in various tissues and cells with strong bioactivities and is the mostly studied activin^[1].
The sequence of amino acids in Activin A proteins from different species is very stable, which leads to the conclusion that in the process of evolution, Activin A has been only slightly altered, and that both in humans and in animals, its function is similar.
Activin exists in three basic molecular forms composed of two inhibin β subunits: activin A (βAβA), activin B (βBβB), and activin AB (βAβB). Activin A binds with high affinity to activin type II receptors, which recruit type I receptors and are necessary for the activation of Smad2/3 signaling. The phosphorylated ActRI activates Smad2 and Smad3, which form a complex with Smad4 to translocate to the nucleus. Activin and TGF-β share the same signaling pathway at the level of Smad2/3/4. Activin A exerts a variety of biological functions including regulation of hematopoietic cell proliferation, neuron differentiation, pituitary hormone secretion, and tissue repair. It is also involved in the process of many diseases, for example, inflammation, fibrosis and tumorigenesis^[1][2].
Activin A has pro- and anti-tumorigenic functions depending on the tumor type. In breast, liver and colon cancers, activin signals were revealed to inhibit tumor cell growth. In addition, tumor tissues were revealed to express decreased levels of activin A or increased levels of activin antagonists or demonstrated the downregulation of activin receptors or Smad proteins. Moreover, its roles include embryonic differentiation, trophoblast invasion of the uterine wall in early pregnancy, and fetal/neonate brain protection in hypoxic conditions. Activin A also regulates bone formation and regeneration, enhances joint inflammation in rheumatoid arthritis, and triggers pathogenic mechanisms in the respiratory system^[1][2].

Recombinant Activin A (0-10 ng/mL; for 12 and 24 h) inhibits the proliferation of myeloma cell line NS-1 cells and induces NS-1 cell apoptosis. Activin A upregulates the expression of CHOP, GADD34, caspase-3, and caspase-12. Moreover, both Smad3 and p-Smad3 levels are increased with treatment of activin A in NS-1 cells^[1].
Recombinant Activin A (1, 5, 50, 100, 200 ng/mL) increases the abundance of specific globin probe fragments for gamma and epsilon globins (209 nucleotides) as well as alpha (180 nucleotides), which are protected from S1 digestion, in the human erythroid cell line, K562^[3].
Recombinant Activin A (50 ng/mL; 6-72 hours) increases the cell content of FSH and total FSH (secreted plus intracellular) in rat pituitary cells^[5].

Recombinant Activin A (20 ng/1 µL; intratumoral injection; for 6 days) inhibits the growth of solid tumors in tumor-bearing mice with NS-1 cells^[1].
Recombinant Activin A (1 μg/20 μL; i.c.v.; once) reduces the neuronal loss in the hippocampal CA1/2 region, dorsolateral striatum but not in the parietal cortex in a 15-min hypoxic-ischemic (HI) injury in the rat brain. Activin A can enhance the survival of injured hippocampal and striatal neurons^[4].

1. The ED₅₀ for this effect is <8 ng/mL, as measured by its ability to inhibit proliferation of MPC-11 cells.
2. The ED₅₀ is less than 8 ng/mL, as measured by its ability to induce SMAD signaling in 293-Activin A Res cells.

• 
  Measured by its ability to inhibition on MPC11 cell proliferation. The ED₅₀ for this effect is typically 0.7508 ng/mL, corresponding to a specific activity is 1.33×10⁶ units/mg.

Human

HEK293

Tag Free

P08476 (G311-S426)

3624  [NCBI]

GLECDGKVNICCKKQFFVSFKDIGWNDWIIAPSGYHANYCEGECPSHIAGTSGSSLSFHSTVINHYRMRGHSPFANLKSCCVPTKLRPMSMLYYDDGQNIIKKDIQNMIVEECGCS

Approximately 13-15 kDa

• 
  Greater than 95% as determined by reducing SDS-PAGE.

Lyophilized powder

Lyophilized from a 0.2 μm filtered solution of 4 mM HCl.

<0.01 EU/μg, determined by LAL method.

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

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]. Ge J, et al. Involvement of CHOP in activin A induced myeloma NS 1 cell apoptosis. Oncol Rep. 2019;42(6):2644-2654.  [Content Brief]

  [2]. Enrrico Bloise, et al. Activin A in Mammalian Physiology. Physiol Rev. 2019 Jan 1;99(1):739-780.  [Content Brief]

  [3]. N L Frigon Jr, et al. Regulation of globin gene expression in human K562 cells by recombinant activin A. Blood. 1992 Feb 1;79(3):765-72.  [Content Brief]

  [4]. D D Wu, et al. Expression of the activin axis and neuronal rescue effects of recombinant activin A following hypoxic-ischemic brain injury in the infant rat. Brain Res. 1999 Jul 24;835(2):369-78.  [Content Brief]

  [5]. B Attardi, et al. Rapid stimulatory effect of activin-A on messenger RNA encoding the follicle-stimulating hormone beta-subunit in rat pituitary cell cultures. Mol Endocrinol. 1990 May;4(5):721-6.  [Content Brief]