Review of the putative cell-surface receptors for alpha-fetoprotein: identification of a candidate receptor protein family

Abstract

The identification of a receptor for alpha-fetoprotein (AFP) has long been sought in the field of medicine. The uptake and endocytosis of AFP by rat tumor cells in 1984 sparked a series of confirmatory reports and the original studies were then extended to include multiple tumor types in rats, mice, and humans. The following year, French investigators partially characterized the binding properties of the AFP receptor, but they were not able to purify the receptor. It was not until 1991-1992 that an AFP receptor was partially purified and characterized from both human monocytes and breast cancer cells. By 1993, a monoclonal antibody had been raised against the AFP receptor produced from a breast cancer extract with claims that the receptor was a widespread (universal) oncofetal biomarker for cancer. However, that receptor has yet to be cloned and/or purified due to its complex multimeric binding interactions and associations. The present report will review the literature of the multiple putative AFP receptors described to date, the cellular uptake and endocytosis of AFP, and the biochemical characterization of these putative cell-surface proteins. In addition, evidence derived from computer modeling, proteolytic degradation patterns, and amino acid sequence analysis will be presented in a proposed identification of a family of multi-ligand binding receptors; this family fits many, if not most, of the criteria required for an AFP receptor. The purposed receptor protein family is tentatively identified as the Scavenger receptors which comprise several classes of single- and double-pass integral transmembrane proteins. Present data do not support the concept that the AFP receptor is a "universal" tumor receptor and/or biomarker.

The alpha-fetoprotein third domain receptor binding fragment: in search of scavenger and associated receptor targets

“…Recent reviews and updates by the present author have proposed the presence of at least two major groups of AFP receptors, namely, (1) the scavenger receptor protein family and (2) the mucin glycoprotein superfamily [10,11]. However, isolated reports of other receptors and binding proteins for AFP have emerged in the literature throughout the last several decades; these include G-coupled chemokine receptors, immune/inflammatory cell receptors, NK receptors and intra-cytoplasmic retinoic acid receptors [12][13][14].…”

Surface FTIR Techniques to Analyze the Conformation of Proteins/ Peptides in H2O Environment

“…Proteins are biological macro-molecules which are involved in various biochemical processes (e.g., oxidative phosphorylation [1,2], DNA replication [3,4], response to stimuli [5,6] and so on [7,8]). All the proteins found in biological systems comprise amino acids as shown in Figure 1 [9][10][11].…”

Nonsecreted cytoplasmic alpha-fetoprotein: a newly discovered role in intracellular signaling and regulation. An update and commentary

“…In both hepatic and circulating cells (monocytes, dendritic cells, phagocytes), the uptake of AFP from the circulation has long been described. That is, AFP can bind to several different kinds of cell surface receptors and taken up into cells via receptor-mediated endocytosis [20][21][22]. The endocytotic process first occurs by AFP binding to invaginated clathrin-coated pits within the receptor/ plasma membrane complex to form receptosome vesicles that pinch off from the plasma membrane [23].…”