The urokinase-type plasminogen activator receptor is a key molecule in the regulation of cell-surface plasminogen
activation and, as such, plays an important role in many normal as well as pathologic processes.Nucleotide sequencing indicated that the complete coding sequence encodes 335 amino acids, including a predicted
signal peptide of 22 residues and a hydrophobic C-terminal portion that is probably cleaved during formation of the GPI
linkage.
NCBI Summary:
This gene encodes the receptor for urokinase plasminogen activator and, given its role in localizing and promoting plasmin formation, likely influences many normal and pathological processes related to cell-surface plasminogen activation and localized degradation of the extracellular matrix. It binds both the proprotein and mature forms of urokinase plasminogen activator and permits the activation of the receptor-bound pro-enzyme by plasmin. The protein lacks transmembrane or cytoplasmic domains and may be anchored to the plasma membrane by a glycosyl-phosphatidylinositol (GPI) moiety following cleavage of the nascent polypeptide near its carboxy-terminus. However, a soluble protein is also produced in some cell types. Alternative splicing results in multiple transcript variants encoding different isoforms. The proprotein experiences several post-translational cleavage reactions that have not yet been fully defined. [provided by RefSeq, Jul 2008]
General function
Receptor
Comment
Cellular localization
Plasma membrane
Comment
Ovarian function
Ovulation, Oogenesis, Oocyte maturation
Comment
Li M et al 1997 reported expression of urokinase-type plasminogen activator and its receptor (uPAR) during ovarian follicular development.
The presence of these proteins in various follicular
cells at different stages of maturation was evaluated by immunolocalization and
ELISA. Abundance of respective messenger RNA in granulosa cells from
preantrallearly antral, midantral and preovulatory follicles and the residual
ovaries was determined by Northern blot analysis. Whereas uPA transcript and
protein levels were highest at the earliest stage of follicular growth examined and
decreased markedly before the expected time of ovulation, the opposite was true
for uPAR. In addition, tPA and PAI-1 messenger RNA abundance and protein
contents were low in both granulosa and residual ovarian tissue during early
follicular development but increased thereafter, reaching highest levels at the
preovulatory period. These findings demonstrate for the first time the presence of
uPAR in ovarian follicles and its developmental expression. The coincidental rise
in uPAR and PAI-1 proteins during the preovulatory period may be important for
the regulation of extracellular matrix remodelling before ovulation. The reciprocal
expression of uPA and tPA during follicular development are consistent with the
notion that these proteases have different biological functions in the ovary, i.e.
tPA is involved in follicular wall remodelling before ovulation whereas uPA is
important in extracellular matrix degradation during cell proliferation and
migration that accompany follicle growth.
Gene whose expression is detected by cDNA array hybridization: transporters, signal transduction Rozenn Dalbis-Tran and Pascal Mermilloda
Expression regulated by
Comment
Canipari et al reported mouse oocytes inhibit plasminogen activator production by ovarian cumulus and granulosa cells. UPA is expressed in mural granulosa but low in cumulus cells.
Concentration of soluble urokinase plasminogen activator receptor (suPAR) in the pre-ovulatory follicular fluid is associated with development of ovarian hyperstimulation syndrome during ovarian stimulation. Grynnerup AG et al. (2018) Investigating whether pre-ovulatory follicular fluid (FF) levels of selected proteins differ between women who do or do not develop severe ovarian hyperstimulation syndrome (OHSS) and evaluate whether they potentially could guide a "freeze-all" strategy. FF was collected during a randomized controlled trial comparing OHSS in antagonist versus agonist protocol including 1050 women in their first assisted reproductive technology (ART) cycle during year 2009-2013. The present sub-study is a matched case-control study comparing FF levels of soluble urokinase plasminogen activator receptor (suPAR), C-reactive protein, placental growth factor, vascular endothelial growth factor, and angiopoietins 1 and 2 in OHSS cases (n = 25, severe OHSS, and ≥ 15 oocytes), high-risk controls (n = 25, no OHSS, and ≥ 15 oocytes), and low-risk controls (n = 25, no OHSS, and 5-8 oocytes). FF level of suPAR differed significantly between the three groups (p = 0.018) with mean (SD) levels of 2.3 (0.4) μg/L, 2.6 (0.8) μg/L, and 2.8 (0.6) μg/L in OHSS cases, high-risk controls, and low-risk controls, respectively. Receiver operating characteristic curve analysis demonstrated that suPAR levels could predict severe OHSS (AUC 0.678; 95% CI 0.553-0.803) with a sensitivity of 64% and a specificity of 66%. None of the other investigated proteins differed between the three groups or between OHSS cases and combined controls. The pre-ovulatory FF level of suPAR was significantly lower in women developing severe OHSS, indicating that the plasminogen activator system could be involved in the pathophysiology of OHSS. However, suPAR did not provide a satisfying predictive value for the prediction of OHSS.//////////////////
Expression and localization of urokinase-type plasminogen activator receptor in bovine cumulus-oocyte complexes. García DC et al. (2015) Urokinase-type plasminogen activator (uPA) is a serine protease involved in extracellular matrix remodeling through plasmin generation. uPA usually binds to its receptor, uPAR, which is anchored to the plasma membrane through a glycosylphosphatidylinositol anchor. uPA/uPAR binding increases proteolytic activity in the neighborhood of the cells containing uPAR and activates intracellular signaling pathways involved in extracellular matrix remodeling, cell migration and proliferation. The aim of this work was to study the expression of uPA, uPAR and plasminogen activator inhibitor-1 (PAI-1) in immature and in vitro matured bovine cumulus-oocyte complexes (COCs). uPA is only expressed in the cumulus cells of immature and in vitro matured COCs, while uPAR and PAI-1 are expressed in both the cumulus cells and the immature and in vitro matured oocytes. In addition, uPAR protein was localized by confocal microscopy in the plasma membrane of oocytes and cumulus cells of immature COCs. Results from this research led us to hypothesize that the uPA/uPAR interaction could cause the local production of uPA-mediated plasmin over oocyte and cumulus cell surface; plasmin formation could also be regulated by PAI-1.//////////////////
Murdoch et al 1999 studied hormonal control of urokinase plasminogen activator secretion by sheep ovarian
surface epithelial cells.
Young TN, et al 1994 reported the coordinate expression of urinary-type plasminogen activator and
its receptor accompanies malignant transformation of the
ovarian surface epithelium.
Overexpression of
urinary-type plasminogen activator is associated with malignant transformation of
the ovarian epithelium. Increased cell surface proteolysis mediated by
urinary-type plasminogen activator bound to cell surface urinary-type plasminogen
activator receptor may contribute to metastatic behavior in ovarian carcinoma.