Multiple forms of mRNA encoding human pregnancy-associated endometrial alpha 2-globulin, a beta-lactoglobulin homologue.

Abstract

Human pregnancy-associated endometrial a2-globulin (a2-PEG) is the major secretory protein product of the endometrium during embryo implantation and the first few weeks of pregnancy. It is a homologue of 8-lactoglobulin, a retinol binding protein, but unlike ig-lactoglobulin it is not found in the mammary gland. The cloning and sequencing of 34 a2-PEG clones has revealed several minor variant forms indicative of alternatively spliced a2-PEG pre-mRNA. These minor forms have also been detected amongs uncloned cDNA after PCR ampfication. Some of these mRNAs would give rise to forms of a2-PEG protein lacking internal sequences, whereas others affect the mRNA sequences on the 3' boundary of the presumed termination codon. Sequences within the cDNA clones are consistent with the existence of splice sites, and together with similarities found between a2-PEG cDNA and ,8-lactoglobulin gene sequences there is good evidence in support of an unusual scheme for the alternative splicing of a2-PEG pre-mRNA involving both alternative 5' splice sites and alternative 3' splice sites. This scheme suggests that the a2-PEG and .3-lactoglobulin genes share a similar structure in at least two regions, and it is likely that 13-lactoglobulin pre-mRNA would show a similar pattern of alternative splicing for one of these regions.

Glycodelin: A Major Lipocalin Protein of the Reproductive Axis with Diverse Actions in Cell Recognition and Differentiation

“…The same sequence was reported for ␣2-PEG (10). The full primary structure of PP14 was first resolved from a decidual cDNA library (18), and essentially the same structure, with some splicing variants, was later confirmed for ␣2-PEG (19). Because PP14 was found to be synthesized in tissues other than endometrium and its molecular mass was not 14 kDa, the name PP14 appeared to be a misnomer.…”

“…Several splicing variants of glycodelin mRNA have been found in the female and male reproductive tracts (19,45) and in hematopoietic cells of the megakaryocytic lineage (52). Some of the variants lack the coding sequences of the glycosylation sites and/or Thr-Asp-Tyr sequence, which is usually found in proteins of the lipocalin family (53).…”

Glycodelins as regulators of early events of reproduction

“…It is now quite obvious that glycodelins are not endometrium-specific, being expressed in other tissues and cells such as seminal vesicles, haematopoietic cells and the ovary (Julkunen et al, 1984;Kämäräinen et al, 1994;Morrow et al, 1994). Thus, glycodelin also refers to various splicing variants and glycoforms of PP14 that may have diverse functions (Morrow et al, 1994;Garde et al, 1991). In this presentation, the term GdA will be used to signify the endometrial type of glycodelin and the name glycodelin-S (GdS) will signify glycodelin from human seminal plasma, which is differentially glycosylated from GdA Morris et al, 1996).…”

Expression of glycodelin in human breast and breast cancer

“…Should this happen, then the resulting protein should lack 1 of the potential glycosylation sites at Asn-85 and 2 cysteinyl residues at 119 and 160, affecting folding. Expression of the splicing variant in normal breast tissue further confirms that glycodelin is not cancer specific since alternatively spliced glycodelin mRNA variants have also been found in the endometrium (Garde et al, 1991), in hematopoietic cells (Morrow et al, 1994) and in seminal vesicles (Koistinen et al, 1997).…”