Abstract
The concept of paracrine/autocrine regulation of cellular mechanisms by peptide regulators acting through cell surface receptors and generating a cascade of intracellular second messengers is highly established. Recent evidence is accumulating that peptide regulatory factors can act within the cell (without plasma membrane signaling receptors) and this action has been coined “intracrine”. The locus of many intracrine actions appears to be the nucleus. Evidence also indicates that insulin-like growth factor binding protein-3 (IGFBP-3) directly interacts with nuclear receptors. We and others have indicated that lactoferrin (Lf) and IGFBP-3 are also intracrine factors and these proteins appear on the putative list of potential intracrine factors. These proteins have a signal sequence and are secreted from cells. Additionally, they have nuclear localization sequences (NLS) and have been shown to sequester in the nuclear compartment of some cells. While IGFBP-3 has been linked to retinoid receptors and signaling, the mechanism of cellular internalization and the resulting phenotypic effect has remained unclear. However, a recent study has indicated that nucleolin may be responsible for Lf binding as well as translocation to the nuclear compartment. We hypothesize that the high regulation, high synthesis and secretion rates of Lf and IGFBP-3 by mammary cells provide the opportunity to be critical regulators of mammary gland development and differentiation via nucleolin and retinoid receptors.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.