Title:Review of the Third Domain Receptor Binding Fragment of Alphafetoprotein (AFP): Plausible Binding of AFP to Lysophospholipid Receptor Targets
Volume: 18
Issue: 7
关键词:
α-甲胎蛋白,结合蛋白,细胞靶点,树突细胞,碎片,溶血磷脂,单细胞/巨噬细胞,受体
摘要: 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.