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Details for messenger / hormone: amphiregulin

EndoNet ID: ENH00315

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Synonyms

  • amphiregulin
  • AR
  • colorectum cell-derived growth factor
  • CRDGF
  • SDGF
  • AREG
  • schwannoma-derived growth factor

General information

  • Amphiregulin and epiregulin belong to the epidermal growth factor family, and act as mitogenic stimulators via binding to EGF receptors. [1]
  • Both an increase in intracellular calcium and activation of PKC lead to activation of an extracellular metalloproteinase that acts on the membrane bound precursors of EGF-receptor ligands including HB-EGF, amphiregulin and TGF-alpha. [2]
  • T helper 2 cells (T(H)2), but not other T cell subsets, express amphiregulin, a member of the epidermal growth factor (EGF) family. [3]
  • AR was first isolated from conditioned medium of MCF-7 human breast carcinoma cells exposed to PMA . It is expressed in vivo by numerous normal human tissues and its expression is regulated by many signals, such as estrogen, androgen, other EGF-like ligands (EGF and TGF-alpha), vitamin D3, and prostaglandin E2 (PGE2). [4]
  • AR up-regulates a number of genes involved in cell motility and invasion in MCF10A cells, suggesting that an AR autocrine loop contributes to the aggressive breast cancer phenotype. [5]

Classification

Hormone function

  • development and growth
    • growth stimulation

    Chemical classification

    • hormone
      • genome-encoded
        • cytokines

    Composition

    Sequence
    SVRVEQVVK PPQNKTESE NTSDKPKRK 
    KKGGKNGKN RRNRKKKNP CNAEFQNFC 
    IHGECKYIE HLEAVTCKC QQEYFGERC 
    GEK
    UniProt P15514

    Links to other resources

    UniProt P15514
    Ensembl ENST00000395748
    KEGG hsa:727738
    • Anatomical structure: osteoblast

      • Amphiregulin (AR) is a potent growth factor for the preosteoblast but it also strongly inhibits osteoblast differentiation. [4]

      Influenced by:

      • PTHR1
        in osteoblast
        • PTH rapidly and strongly stimulates the expression of amphiregulin not only in several osteoblastic cell lines but also in bone. [4]
      • EP3
        in osteoblast
        • In addition to PTH, PGE2 also strongly stimulates AR expression through the CREB phosphorylation pathway. [4]
      • EP4
        in osteoblast
        • In addition to PTH, PGE2 also strongly stimulates AR expression through the CREB phosphorylation pathway. [4]
    • Anatomical structure: lung

      Influenced by:

      • IGF-1R
        in lung
        • Apoptosis inhibition by amphiregulin through an IGF1-dependent survival pathway in non-small cell lung cancer (NSCLC) cells: amphiregulin activates the IGF1 receptor that in turn induces the secretion of amphiregulin and IGF1. [6]

    Targets

    CellADAM17CD9 antigenEGFR isoform a
    astrocyte Present
    brain Present
    cerebellar cortex Present
    cerebral cortex Present
    continuous vascular endothelial cell of blood vessels and lymphatics Present
    Phenotypes
    • regulation of angiogenesis
    digestive system Present
    epithelial cell Present
    epithelial cell with microvilli Present
    Influences
    • mucin-2
    G cell Present
    Influences
    • gastrin
    hepatocyte Present
    Influences
    • IL-1 alpha
    • IL-1 beta
    hippocampus Present
    keratinocyte Present
    lipocyte of liver Present
    Phenotypes
    • positive regulation of cell proliferation and apotosis
    lung Present
    macrophage Present
    monocyte Present
    Phenotypes
    • ectodomain shedding
    neuron Present
    neutrophil granulocyte Present
    Phenotypes
    • ectodomain shedding
    Present
    Influences
    • IL-8
    placenta Present
    T-lymphocyte Present
    Phenotypes
    • ectodomain shedding
    uterus Present
    Reference