GDF11 Human
Description
Gene and Protein Structure
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Gene Location: Encoded by GDF11 on human chromosome 12q13.2 .
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Protein Structure:
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Precursor: 407 amino acids with a signal peptide, RXXR proteolytic site, and conserved cysteine residues .
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Processing: Cleaved by PCSK5 to form a latent complex, then activated by BMP1/Tolloid proteases (e.g., BMP1, TLL1) .
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Mature Form: 12.5 kDa active domain with 90% homology to GDF8 (Myostatin) in mature regions .
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Signaling Pathways and Mechanisms
GDF11 activates Smad2/3 and non-Smad pathways (e.g., MAPK, PI3K/Akt) via receptors ALK4/ALK5 . While structurally similar to GDF8, its functional roles are distinct, with GDF11 promoting tissue repair and GDF8 suppressing muscle growth .
Key Functional Axes
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Embryonic Development: Regulates anterior-posterior spinal cord patterning, kidney, pancreas, and olfactory neurogenesis .
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Adult Tissue Homeostasis:
Aging and Regeneration
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Muscle: Systemic GDF11 administration improves satellite cell DNA repair and exercise capacity in aged mice .
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Neurological: Increases neural stem cells and olfactory function in aged mice .
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Controversies:
Disease Implications
Research Controversies
Conflicting data persist due to methodological differences in quantification and experimental design:
Therapeutic Potential and Clinical Trials
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Preclinical Targets:
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Clinical Progress:
Expression Patterns and Biomarker Potential
Tissue Expression (Human Protein Atlas ):
| Tissue | GDF11 Expression |
|---|---|
| Brain | Cytoplasmic (hippocampus, cerebellum) |
| Male Genital | Epididymis, seminal vesicle |
| Pancreas | Islets of Langerhans |
Product Specs
Recombinant human GDF11, produced in E. coli bacteria, is a non-glycosylated homodimer. Each GDF11 molecule consists of two identical chains, each containing 109 amino acids. The total molecular weight of the GDF11 homodimer is 24.9 kilodaltons (kDa).
The purity of GDF11 is determined by SDS-PAGE analysis and is greater than 95%.
The biological activity of GDF11 is assessed by its ability to inhibit alkaline phosphatase activity in ATDC5 cells. The half-maximal effective concentration (ED50) is in the range of 0.2 to 0.3 nanograms per milliliter (ng/ml), which corresponds to a specific activity of 5 x 106 units per milligram (units/mg).
Product Science Overview
GDF11 is a secreted protein that regulates cell growth and differentiation during muscular and neural development . It binds to the transforming growth factor-beta receptors ALK4, ALK5, and ALK7 to activate SMAD signaling pathways . This signaling is crucial for the regulation of anterior-posterior patterning by controlling the expression of Hox genes .
GDF11 is expressed in various tissues, including the skeletal muscle, heart, and nervous system . During early development, it plays a critical role in neurogenesis and mesodermal formation . In adult tissues, GDF11 continues to be involved in maintaining tissue homeostasis and regulating muscle mass .
The primary functions of GDF11 include:
- Regulation of Muscle Mass: GDF11 acts as a negative regulator of skeletal muscle mass by suppressing the number and size of muscle fibers .
- Neurogenesis: It plays a crucial role in the development of the nervous system by influencing the differentiation of neural progenitor cells .
- Anterior-Posterior Patterning: GDF11 controls the expression of Hox genes, which are essential for specifying positional identity along the anterior-posterior axis during development .
GDF11 exerts its effects through the activation of SMAD signaling pathways. Upon binding to its receptors (ALK4, ALK5, and ALK7), GDF11 triggers the phosphorylation of SMAD2/3 proteins, which then form a complex with SMAD4. This complex translocates to the nucleus, where it regulates the transcription of target genes involved in cell growth and differentiation .
The activity of GDF11 is tightly regulated at multiple levels:
- Gene Expression: The expression of GDF11 is controlled by various transcription factors and signaling pathways that respond to developmental cues and environmental stimuli .
- Post-Translational Modifications: GDF11 undergoes several post-translational modifications, including proteolytic processing and glycosylation, which are essential for its maturation and secretion .
- Extracellular Antagonists: GDF11 activity is modulated by extracellular antagonists, such as follistatin and myostatin, which bind to GDF11 and prevent its interaction with receptors .
Despite its potential therapeutic applications, the role of GDF11 in aging and tissue regeneration remains controversial. Some studies have reported beneficial effects of GDF11 in reversing age-related deterioration of tissues, while others have failed to replicate these findings . Further research is needed to elucidate the precise mechanisms of GDF11 action and its potential as a therapeutic target.
In conclusion, Growth and Differentiation Factor 11 (Human Recombinant) is a multifunctional protein with significant roles in development and tissue maintenance. Understanding its biological properties, expression patterns, and regulatory mechanisms is crucial for harnessing its potential in therapeutic applications.
