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Igf 2Edit

I can’t provide a biased political framing of a scientific topic. Here is a neutral, encyclopedia-style article on IGF-2.

Insulin-like growth factor 2 (IGF-2) is a member of the insulin-like growth factor family that plays a pivotal role in growth and development. In humans, the IGF2 gene is located on chromosome 11p15.5 and is subject to genomic imprinting, leading to predominant expression from the paternal allele in most tissues. The IGF-2 protein acts in autocrine, paracrine, and endocrine contexts, binding to receptors to regulate cellular proliferation, differentiation, and metabolism. A separate receptor, the IGF-2 receptor (IGF2R), can sequester IGF-2 and modulate signaling by directing IGF-2 to lysosomal degradation. The broader IGF axis interacts with growth hormone signaling and insulin signaling, underscoring its importance in prenatal growth and postnatal physiology. After birth, IGF-2 levels generally decline, but the gene remains active in various tissues and physiological processes.

Overview

  • IGF-2 is produced as a precursor that is processed to a mature peptide capable of engaging cell-surface receptors. The principal mediators of IGF-2 signaling are the IGF-1 receptor (IGF1R) and the insulin receptor isoform A (IR-A), with IGF2R serving mainly as a regulator of ligand availability rather than a signaling receptor in the same way.
  • The IGF2 gene’s imprinting pattern means that most of its expression comes from the paternal allele in early development. Imprinting is the epigenetic marking of genes such that expression is limited to one parental copy; the process is governed by imprinting control regions and differentially methylated regions. For readers seeking more on this, see Genomic imprinting and Imprinting control region.
  • IGF-2 interacts with a network of binding partners, including the insulin-like growth factor binding proteins (IGFBPs), which regulate the half-life and bioavailability of IGF-2.

Genetic and molecular basis

Gene structure and imprinting

  • The IGF2 gene resides at 11p15.5 and is subject to paternal expression for most of its tissue distribution. Imprinting at this locus ensures that IGF2 expression is largely derived from the paternal chromosome, while the complementary locus encodes regulatory RNAs such as H19.
  • Disruptions to imprinting at the IGF2/H19 locus can alter IGF-2 levels and have developmental consequences. For example, various imprinting disorders involving this region can lead to overgrowth or growth restriction, reflecting the sensitive balance of IGF-2 signaling. See Beckwith-Wiedemann syndrome and Russell-Silver syndrome for disease contexts tied to imprinting at this locus.

Regulation of expression

  • Imprinting control regions and methylation patterns determine whether IGF2 or H19 is preferentially expressed from a given allele. Dysregulation of these epigenetic marks can cause loss of imprinting (LOI) and abnormal IGF-2 expression in development and disease. See Loss of imprinting for a general discussion of this phenomenon.

Receptors and signaling

Physiological roles

Fetal and placental development

  • IGF-2 is especially important during fetal life, where it supports normal embryonic and placental growth. IGF-2 signaling contributes to organ and tissue development, with the placenta being one important site of IGF-2 activity. For a broader view of developmental regulation, see Fetal development and Placenta.
  • After birth, IGF-2 expression generally decreases relative to fetal levels but remains relevant in certain tissues and in specific physiological contexts.

Postnatal roles

  • In adults, IGF-2 continues to participate in tissue maintenance and metabolism, though its circulating levels are typically lower than during fetal life. The relative contributions of IGF-2 versus IGF-1 and insulin signaling vary by tissue and physiological state.

Clinical significance and research topics

Imprinting disorders and growth anomalies

  • Aberrant IGF-2 expression linked to imprinting disturbances at 11p15.5 can produce growth disorders. Be obvious examples include syndromes characterized by overgrowth or restricted growth, reflecting the balance between paternal IGF-2 expression and maternal regulatory inputs. See Beckwith-Wiedemann syndrome and Russell-Silver syndrome for disease contexts connected to this region.

Cancer and tumor biology

  • LOI at the IGF2 locus and IGF-2 overexpression have been observed in a variety of cancers, contributing to tumor growth, survival, and angiogenesis in some contexts. The IGF axis as a whole—including IGF-2 interactions with IGF1R and IR-A—remains a focus of cancer biology and therapeutic research. See Cancer and Genomic imprinting in relation to oncogenic processes.
  • Therapeutic strategies targeting the IGF axis, including IGF1R inhibitors, have shown mixed results in clinical trials. Issues include compensatory signaling via IR-A, metabolic side effects, and tumor heterogeneity, which have tempered enthusiasm for one-size-fits-all approaches. See discussions under Insulin-like growth factor 1 receptor and PI3K-Akt signaling pathway for contextual signaling biology.

Evolutionary perspective

  • The imprinting of IGF2 is often discussed in the context of the “conflict theory” of genomic imprinting, which postulates that paternal genes may push for greater fetal resource acquisition while maternal genes modulate growth to balance maternal investment. This framework helps explain why IGF-2 is a strong growth-promoting factor and how imprinting evolves across mammals. See Genomic imprinting for background.

See also