The insulin like growth factors (IGFs) are the major growth- promoting factors in plasma. IGFs are secreted by a variety of cells and exert a multitude of effects on cellular survival, growth and differentiation. The A and B domains of IGFs are identical to insulin. IGF initiates their biological action through binding to the type IGF receptor (IGF-1R), a heterotrimeric protein complex with a tyrosine kinase activity. The IGF-IIR lacks the kinase activity and is actually identical to the mannose-6-phophate receptor. Unlike most other peptide hormones, IGFs are complexed with specific binding proteins in the plasma known as IGF Binding proteins (IGFBPs). These proteins are present in plasma in high concentration as compared to the membrane IGFRs. Therefore, IGFBPs have the potential to modulate the IGF action. IGFBPs have been shown to either inhibit or stimulate the IGF effects. The primary structures of mammalian IGFBPs appear to contain three distinct domains of roughly equivalent sizes: the conserved N-terminal domain, the highly variable mid region and the conserved C-terminal domain. Human IGFBPs share ~36% identity. IGFBP4 (aa22-237 mature protein, Accession # P22692) is expressed in multiple tissues including adrenal, testis, spleen, heart, lung, kidney, liver, stomach, hypothalamus and brain cortex. High expression levels are found in the non-paranchymal cells of the liver. IGFBP4 is expressed by human osteoblast-like cells and is also expressed in skin fibroblasts.
Intended for research use only. Not for use in human, therapeutic, or diagnostic applications.