Review of the Third Domain Receptor Binding Fragment of Alphafetoprotein (AFP): Plausible Binding of AFP to Lysophospholipid Receptor Targets

Author(s): Gerald J. Mizejewski*.

Journal Name: Current Drug Targets

Volume 18 , Issue 7 , 2017

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Abstract:

Alpha-fetoprotein (AFP) is a 69 kD fetal- and tumor-associated single-chain glycoprotein belonging to the albuminoid gene family. AFP functions as a carrier/transport molecule as well as a growth regulator and has been utilized as a clinical biomarker for both fetal defects and cancer growth. Lysophospholipids (LPLs) are plasma membrane-derived bioactive lipid signaling mediators composed of a small molecular weight single acyl carbon chain (palmitic, oleic acid) attached to a polar headgroup; they range in molecular mass from 250-750 daltons. The LPLs consist of either sphingosine-1-phosphate or lysophosphatidic acid, and mostly their choline, ethanolamine, serine or inositol derivatives. They are present only in vertebrates. These bioactive paracrine lipid mediators are ubiquitously distributed in tissues and are released from many different cell types (platelets, macrophages, monocytes, etc.) involved in developmental, physiological, and pathological processes. The LPLs bind to four different classes of G-protein coupled receptors described herein which transduce a multiple of cell effects encompassing activities such as morphogenesis, neural development, angiogenesis, and carcinogenesis. The identification of potential binding sites of LPL receptors on the AFP third domain receptor binding fragment was derived by computer modeling analysis. It is conceivable, but not proven, that AFP might bind not only to the LPL receptors, but also to LPLs themselves since AFP binds medium and long chain fatty acids. It is proposed that some of the activities ascribed to AFP in the past might be due in part to the presence of bound LPLs and/or their receptors.

Keywords: Alpha-fetoprotein, binding proteins, cell targets, dendritic cells, fragments, lysophospholipids, monocytes /macrophages, receptors.

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Article Details

VOLUME: 18
ISSUE: 7
Year: 2017
Page: [874 - 886]
Pages: 13
DOI: 10.2174/1389450117666160201105245
Price: $58

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