GO:1990418 response to insulin-like growth factor stimulus: Signaling Pathway, Genes, Functions and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:1990418 describes any cellular or organismal change (movement, secretion, enzyme production, gene expression) triggered by an insulin-like growth factor (IGF) stimulus [1, 4].
• IGF-1 is a key mediator of growth hormone effects, promoting bone formation, muscle growth, and cartilage maintenance [2, 6, 8].
• The response involves IGF-1 binding to IGF-1R, activation of downstream signaling (e.g., PI3K/AKT, MAPK), and altered gene expression [3, 6].
• Deficiencies in IGF-1 signaling cause growth failure and metabolic disorders in humans.
• IGF-1 signaling is implicated in cancer progression, bone metastasis pain, and renal cell carcinoma [3, 7].
• Experimental models include knockout mice, point-mutant cell lines, and engineered IGF-1 variants for local delivery [5, 6].
Description
The Gene Ontology (GO) term GO:1990418, response to insulin-like growth factor stimulus, defines the cellular and organismal processes that occur following exposure to insulin-like growth factors (IGFs), such as IGF-1 and IGF-2 [1, 4]. This term encompasses changes in cell movement, secretion, enzyme production, and gene expression that are triggered by IGF stimulation. IGFs are polypeptide hormones structurally related to insulin and play critical roles in growth, development, and metabolism. The response to IGF stimulus is essential for normal physiology, including bone formation, muscle hypertrophy, and cartilage homeostasis [2, 6, 8]. Dysregulation of this response is associated with human diseases such as growth deficiency, cancer, and chronic pain [3, 4, 7]. Researchers study GO:1990418 to understand how cells interpret and respond to IGF signals, and to identify therapeutic targets for related disorders [3, 5].
response to insulin-like growth factor stimulus At A Glance
| GO ID | GO:1990418 |
|---|---|
| GO term | response to insulin-like growth factor stimulus |
| Ontology | biological_process |
| Synonym | None |
| Major function | Mediates cellular and organismal changes in response to IGF stimulation, including growth, metabolism, and gene expression [1, 4] |
| Key ligands | IGF-1, IGF-2 |
| Key receptors | IGF-1R, insulin receptor [3, 6] |
| Downstream pathways | PI3K/AKT, MAPK/ERK [3, 6] |
| Physiological outcomes | Bone formation, muscle growth, cartilage maintenance [2, 6, 8] |
What Is GO:1990418?
GO:1990418 is a biological process term that describes any change in a cell or organism's state or activity as a result of an insulin-like growth factor stimulus. This includes alterations in movement, secretion, enzyme production, gene expression, and other cellular activities. The term captures the downstream effects of IGF binding to its receptors and the subsequent signaling cascades that lead to physiological responses [1, 4].
Why Is response to insulin-like growth factor stimulus Important in Cell Biology?
Understanding GO:1990418 is crucial because IGF signaling is a central regulator of growth, metabolism, and tissue repair, and its dysregulation contributes to a wide range of human diseases, including growth disorders, cancer, and metabolic syndromes [4, 7]. Experimental models targeting this process help elucidate mechanisms of development and disease, and inform therapeutic strategies such as engineered IGF-1 for local delivery.
• IGF-1 is essential for postnatal growth and bone formation [2, 4].
• The response to IGF stimulus regulates muscle growth and regeneration.
• IGF-1 signaling maintains articular cartilage and responds to mechanical compression.
• Dysregulated IGF signaling is implicated in cancer, including renal cell carcinoma.
• IGF-1R in Schwann cells mediates metastatic bone cancer pain.
• Human IGF-1 deficiency causes growth failure and metabolic complications.
• Engineered IGF-1 variants enable targeted local delivery for therapeutic applications.
• Resistance exercise modulates hormonal responses including IGF-1.
• Gut microbiota can induce IGF-1 to promote bone growth.
• IGF-1 signaling is a target for treating growth disorders and tissue degeneration [4, 5].
What Happens During response to insulin-like growth factor stimulus?
IGF Binding and Receptor Activation
In simple terms: IGF binds to its receptor on the cell surface, like a key fitting a lock, to start a signal inside the cell.
The response begins when insulin-like growth factor (IGF-1 or IGF-2) binds to the insulin-like growth factor 1 receptor (IGF-1R) or insulin receptor on the cell membrane [3, 6]. This binding activates the receptor's intrinsic tyrosine kinase activity, leading to autophosphorylation and recruitment of adaptor proteins such as IRS-1. In Schwann cells, IGF-1R activation is required for pain signaling in bone cancer. Myoferlin, a membrane protein, is also required for IGF response in muscle cells.
Intracellular Signaling Cascades
In simple terms: Once activated, the receptor triggers a chain of molecular signals inside the cell that tell it to grow, divide, or change its behavior.
Activated IGF-1R phosphorylates IRS proteins, which then activate the PI3K/AKT and MAPK/ERK pathways [3, 6]. These cascades regulate gene expression, protein synthesis, and cell survival. In muscle, IGF-1 promotes growth via AKT-mediated signaling, and myoferlin is necessary for this response. In cartilage, dynamic compression enhances IGF-1 response, likely through mechanotransduction pathways.
Gene Expression and Cellular Responses
In simple terms: The signals reach the nucleus and switch genes on or off, leading to changes like growth, division, or secretion.
Downstream signaling activates transcription factors such as FOXO and mTOR, altering gene expression to promote anabolic processes. This results in increased protein synthesis, cell proliferation, and differentiation. For example, IGF-1 induces bone formation by stimulating osteoblast activity. In renal cell carcinoma, IGFBP5, a modulator of IGF signaling, is a probable target.
Physiological Outcomes
In simple terms: The final result is a change in the body, such as stronger bones, bigger muscles, or repaired cartilage.
The integrated response to IGF stimulus leads to tissue-specific outcomes: bone growth and mineralization, muscle hypertrophy, and cartilage matrix maintenance. In pathological contexts, it can promote cancer cell survival or mediate bone cancer pain. Human IGF-1 deficiency results in growth retardation and metabolic dysfunction.
Key Genes Involved in GO:1990418 response to insulin-like growth factor stimulus
The following genes and proteins are central to the response to insulin-like growth factor stimulus, based on experimental evidence from the cited literature.
| Gene | Major Role | Research Relevance |
|---|---|---|
| IGF1 | Ligand that binds IGF-1R to initiate signaling | Deficiency causes growth failure; engineered for local delivery [4, 5] |
| IGF1R | Receptor tyrosine kinase that mediates IGF-1 signaling | Target in cancer pain and growth disorders |
| IGF2 | Fetal growth factor that also binds IGF-1R | Implicated in growth and cancer |
| INSR | Insulin receptor that can form hybrids with IGF-1R | Cross-talk in metabolic signaling |
| IRS1 | Adaptor protein downstream of IGF-1R | Mediates PI3K/AKT activation |
| IRS2 | Adaptor protein in IGF signaling | Regulates metabolism and growth |
| AKT1 | Serine/threonine kinase in PI3K pathway | Promotes cell survival and growth |
| MAPK1 | ERK2 kinase in MAPK pathway | Regulates proliferation and differentiation |
| MYOF | Myoferlin, membrane protein required for IGF response | Muscle growth and repair |
| IGFBP5 | IGF-binding protein that modulates IGF availability | Target in renal cell carcinoma |
| IGFBP3 | Major IGF carrier protein in circulation | Regulates IGF bioavailability |
| IGFBP1 | Modulates IGF action in metabolic tissues | Linked to insulin resistance |
| GHR | Growth hormone receptor, upstream of IGF-1 production | Deficiency causes Laron syndrome |
| STAT5B | Transcription factor mediating GH-induced IGF-1 expression | Mutations cause growth failure |
| SOCS2 | Negative regulator of GH/IGF-1 signaling | Knockout enhances growth |
| PAPP-A | Protease that releases IGF from IGFBP complexes | Regulates local IGF availability |
| FGFR3 | Fibroblast growth factor receptor 3, interacts with IGF signaling | Cartilage growth regulation |
How Is response to insulin-like growth factor stimulus Regulated?
The response to IGF stimulus is tightly regulated at multiple levels. IGF bioavailability is controlled by IGF-binding proteins (IGFBPs), which sequester IGFs in the circulation and extracellular matrix [4, 7]. Proteases such as PAPP-A cleave IGFBPs to release active IGF. Receptor activation is modulated by phosphatase activity and internalization. Downstream, negative feedback loops involving SOCS proteins and phosphatases attenuate signaling. Mechanical loading can also modulate the response, as dynamic compression enhances IGF-1 effects in cartilage.
response to insulin-like growth factor stimulus and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| IGF1 | IGF-1 deficiency, growth failure | Igf1 knockout mouse, patient iPSCs |
| IGF1R | Bone cancer pain, cancer progression | Schwann cell-specific knockout, xenograft models |
| IGFBP5 | Renal papillary cell carcinoma | Knockdown/overexpression in RCC cell lines |
| MYOF | Muscle growth defects | Myof knockout mouse, C2C12 myoblasts |
| PAPP-A | Cartilage degeneration | Pappa knockout mouse, chondrocyte cultures |
IGF-1 Deficiency and Growth Disorders
Human conditions of IGF-1 deficiency, including mutations in the IGF1 gene or upstream growth hormone signaling components, lead to severe postnatal growth failure, short stature, and metabolic abnormalities. These conditions highlight the essential role of GO:1990418 in normal development. Experimental models include Igf1 knockout mice and patient-derived cell lines.
Cancer and Metastasis
Dysregulated IGF signaling promotes tumor growth and survival. In renal papillary cell carcinoma, IGFBP5 is a probable target, suggesting a role in tumorigenesis. In bone cancer pain, IGF-1R in Schwann cells mediates metastatic pain, indicating that IGF signaling in the tumor microenvironment contributes to cancer morbidity. Targeting IGF-1R or its ligands is a therapeutic strategy [3, 7].
Musculoskeletal and Cartilage Disorders
IGF-1 is critical for muscle growth and repair; myoferlin deficiency impairs IGF response and muscle growth. In articular cartilage, IGF-1 maintains matrix integrity, and dynamic compression enhances this response, suggesting that mechanical loading and IGF signaling interact in joint health. Defects in these processes contribute to sarcopenia and osteoarthritis [6, 8].
From response to insulin-like growth factor stimulus-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does IGF1 loss cause growth retardation? | Igf1 knockout mouse |
| Is IGF-1R required for bone cancer pain? | Schwann cell-specific Igf1r knockout mouse |
| Does myoferlin mediate IGF response in muscle? | Myof knockout mouse and C2C12 cells |
| Can engineered IGF-1 improve local delivery? | Point-mutant IGF-1 knock-in mouse |
| How does mechanical compression affect IGF response? | Cartilage explants with dynamic compression |
| Does IGFBP5 promote renal cell carcinoma? | IGFBP5 overexpression/knockdown in RCC lines |
How to Study the response to insulin-like growth factor stimulus Process
| Method | What It Measures | Typical Application |
|---|---|---|
| RNA-seq | Global gene expression changes | Identify IGF-induced transcripts |
| Phosphoproteomics | Phosphorylation events | Map signaling cascades |
| Western blot | Protein levels and phosphorylation | Validate AKT/ERK activation |
| Alizarin Red staining | Bone mineralization | Osteoblast differentiation |
| Glycosaminoglycan assay | Cartilage matrix production | Chondrocyte response |
| Micro-CT | Bone density and structure | In vivo bone growth |
| Pain behavior assays | Nociceptive responses | Bone cancer pain models |
Transcriptomic and Proteomic Profiling
RNA-seq and proteomics can identify global changes in gene and protein expression following IGF stimulation. For example, IGF-1 treatment alters transcript levels in osteoblasts and muscle cells [2, 6]. These methods help define the downstream effectors of GO:1990418.
Phosphoproteomics and Signaling Assays
Phosphoproteomics and Western blotting for phospho-AKT and phospho-ERK are used to monitor immediate signaling events after IGF-1R activation [3, 6]. These techniques quantify pathway activation and identify feedback mechanisms.
Functional Assays for Growth and Differentiation
Cell proliferation, differentiation, and matrix production assays (e.g., Alizarin Red for bone, glycosaminoglycan for cartilage) measure physiological outcomes of IGF response [2, 8]. Muscle hypertrophy can be assessed by myotube diameter.
In Vivo Models and Imaging
Genetically modified mice and imaging techniques (micro-CT for bone, MRI for muscle) allow assessment of IGF responses in vivo [2, 4]. Pain behavior assays in bone cancer models evaluate sensory outcomes.
How CRISPR Can Be Used to Study GO:1990418 response to insulin-like growth factor stimulus
Knockout
CRISPR knockout of IGF1, IGF1R, or downstream effectors (e.g., IRS1, AKT1) can abolish or reduce the response to IGF stimulus, providing causal evidence for their roles [3, 6]. For example, Igf1r knockout in Schwann cells attenuates bone cancer pain.
Point Mutation
Point mutations can mimic human disease variants or disrupt specific phosphorylation sites. For instance, introducing kinase-dead mutations in IGF1R or mutations in IGF1 that affect receptor binding can dissect signaling mechanisms [4, 5].
Knock-in
Knock-in of tagged or reporter alleles (e.g., GFP-IGF1R) allows visualization and tracking of the receptor in live cells. Knock-in of human disease mutations into mouse models can recapitulate growth disorders.
Overexpression
Overexpression of IGF1 or constitutively active IGF1R can enhance the response, promoting growth or tumorigenesis. This approach is useful for studying gain-of-function effects in cancer and tissue growth.
How EDITGENE Supports response to insulin-like growth factor stimulus Research
Researchers studying response to insulin-like growth factor stimulus-related genes often need to determine whether a candidate gene is causally involved in the signaling cascade, growth outcomes, or disease pathology. EDITGENE provides comprehensive CRISPR-based services to generate precisely engineered cell and animal models, enabling rigorous functional validation of genes within GO:1990418.
Contact EDITGENE today to design your custom CRISPR model for response to insulin-like growth factor stimulus research.
Frequently Asked Questions About response to insulin-like growth factor stimulus
What is GO:1990418?
GO:1990418 is a Gene Ontology term for 'response to insulin-like growth factor stimulus', describing any cellular or organismal change triggered by IGFs [1, 4].
What genes are involved in response to insulin-like growth factor stimulus?
Key genes include IGF1, IGF1R, IRS1, AKT1, MAPK1, and MYOF, among others [3, 4, 6].
What diseases are associated with defective IGF signaling?
IGF-1 deficiency causes growth failure; dysregulated signaling is linked to cancer, bone pain, and cartilage disorders [3, 4, 7, 8].
How does IGF-1 activate cells?
IGF-1 binds to IGF-1R, activating its tyrosine kinase and downstream PI3K/AKT and MAPK pathways [3, 6].
What is the role of myoferlin in IGF response?
Myoferlin is required for IGF-1-induced muscle growth and signaling.
Can IGF-1 be used therapeutically?
Engineered IGF-1 for local delivery is being explored for tissue repair and growth disorders.
How is IGF signaling regulated?
It is regulated by IGF-binding proteins, proteases, and feedback loops involving SOCS proteins [4, 7, 8].
What model systems study IGF response?
Knockout mice, cell lines, and engineered IGF-1 variants are commonly used [2, 3, 5, 6].
Does mechanical compression affect IGF response in cartilage?
Yes, dynamic compression enhances the response of articular cartilage to IGF-1.
What methods measure IGF pathway activation?
Phosphoproteomics, Western blot, and RNA-seq are standard methods [2, 3, 6].
Conclusion
GO:1990418, response to insulin-like growth factor stimulus, is a fundamental biological process that governs growth, metabolism, and tissue homeostasis. Its dysregulation underlies numerous diseases, from growth failure to cancer. Continued research using advanced CRISPR models and multi-omics approaches will further elucidate the mechanisms and therapeutic potential of targeting this pathway [4, 5, 7].
References
- 1. Kraemer WJ et al.. 2005. Hormonal responses and adaptations to resistance exercise and training.. Sports Med 35(4):339-61 PMID: 15831061
- 2. Yan J et al.. 2016. Gut microbiota induce IGF-1 and promote bone formation and growth.. Proc Natl Acad Sci U S A 113(47):E7554-E7563 PMID: 27821775
- 3. Landini L et al.. 2023. Schwann cell insulin-like growth factor receptor type-1 mediates metastatic bone cancer pain in mice.. Brain Behav Immun 110:348-364 PMID: 36940752
- 4. Puche JE et al.. 2012. Human conditions of insulin-like growth factor-I (IGF-I) deficiency.. J Transl Med 10:224 PMID: 23148873
- 5. Tokunou T et al.. 2008. Engineering insulin-like growth factor-1 for local delivery.. FASEB J 22(6):1886-93 PMID: 18285400
- 6. Demonbreun AR et al.. 2010. Myoferlin is required for insulin-like growth factor response and muscle growth.. FASEB J 24(4):1284-95 PMID: 20008164
- 7. Wang S et al.. 2019. Insulin-Like Growth Factor Binding Protein 5-A Probable Target of Kidney Renal Papillary Renal Cell Carcinoma.. Biomed Res Int 2019:3210324 PMID: 31886201
- 8. Bonassar LJ et al.. 2001. The effect of dynamic compression on the response of articular cartilage to insulin-like growth factor-I.. J Orthop Res 19(1):11-7 PMID: 11332605
