IGFBP-3
IGFBP-3 (insulin-like growth factor-binding protein 3, also known as IBP3 or BP-53) is a multifunctional secreted protein that controls the availability of IGF1 and IGF2 to their receptors. It also has IGF-independent antiproliferative and apoptotic activity. Browse Assay Genie's current range of IGFBP-3 research reagents below, or read on for the biology behind the target.
IGFBP-3 plays a critical role in regulating how much IGF1 and IGF2 reaches their receptors, and through this it shapes IGF-mediated cellular processes including proliferation, differentiation and apoptosis, in a cell-type specific manner. In plasma it forms a ternary complex with the insulin-like growth factor acid-labile subunit (IGFALS) and either IGF-I or IGF-II. In this form it circulates, prolonging the half-life of the IGFs and altering their interaction with cell surface receptors.
The protein also acts independently of IGFs. It exerts antiproliferative and apoptotic effects through its receptor TMEM219 (IGFBP-3R), and it signals through LRP-1/alpha2M receptor, also known as the TGF-beta type V receptor, to inhibit cell growth independently of IGF1. Mechanistically, ligation of its receptor induces serine-specific dephosphorylation of IRS1 or IRS2, leading to an inhibitory cascade. IGFBP-3 inhibits the positive effect of humanin on insulin sensitivity and promotes testicular germ cell apoptosis. In the nucleus it interacts with transcription factors such as retinoid X receptor-alpha (RXRA) to regulate transcriptional signalling and apoptosis.
The IGFBP3 gene encodes a member of the IGFBP family, with an IGFBP domain and a thyroglobulin type-I domain. Alternate transcriptional splice variants encoding different isoforms have been characterised. The protein is found both in the secreted compartment and in the nucleus. Orthologues are annotated in mouse and rat (both Igfbp3). Other family members include IGFBP-1, IGFBP-2, IGFBP-4, IGFBP-5, IGFBP-6 and IGFBP-7.
IGFBP-3 regulates the availability of IGF1 and IGF2 to their receptors, making it central to studies of IGF-mediated cell responses.
IGFBP-3 has IGF-independent antiproliferative and apoptotic effects mediated by TMEM219, and growth inhibition via LRP-1/alpha2M receptor.
IGFBP-3 inhibits the positive effect of humanin on insulin sensitivity and induces dephosphorylation of IRS1 and IRS2.
In the nucleus IGFBP-3 interacts with transcription factors such as RXRA to regulate transcriptional signalling and apoptosis.
IGFBP-3 regulates the availability of IGF1 and IGF2 to their receptors, influencing proliferation, differentiation and apoptosis. In plasma it forms a ternary complex with IGFALS and an IGF, prolonging IGF half-life. It also has IGF-independent antiproliferative and apoptotic effects through TMEM219.
IGFBP-3 is encoded by the IGFBP3 gene and is also called IBP3 or BP-53. Its full name is insulin-like growth factor-binding protein 3. Alternate transcriptional splice variants encoding different isoforms have been characterised, so check the datasheet of any product for its validated reactivity.
Yes. Mouse and rat both have an orthologous gene, Igfbp3, so the protein can be studied in common rodent models. IGFBP-3 belongs to the wider IGFBP family, which also includes IGFBP-1, -2, -4, -5, -6 and -7. Check the datasheet of any product for its validated reactivity.
Other members of the IGFBP family that regulate IGF signalling.
Gene and protein annotations from HGNC, NCBI Gene and UniProt P17936; product specifications from Assay Genie datasheets.