Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Primary cultures of peripheral lung lobes were grown in a highly supplemented medium. Human lung endothelial cells (HLE) were isolated from the mixed population by FACS. The cells proliferated rapidly and were serially cultivated for at least 16 passages. Both early and late passage cells were positive for the standard endothelial markers. Factor VIII related-antigen (Factor VIII R-Ag), angiotensin-converting enzyme, acetylated low-density lipoprotein labeled with 1,1'-dioctadecyl-1,3,3,3',3'-tetramethyl-indocarbocyanine perchlorate (DiI-Ac-LDL) uptake, and bound the lectin Ulex europaeus agglutinin (UEA). Prostaglandin E2 was the major cyclooxygenase product of HLE, in contrast to human umbilical vein endothelial cells (HUVE), which synthesized PGI2 in excess of PGE2. Factor VIII R-Ag exhibited a diffuse cytoplasmic as well as an extracellular fibrillar distribution in HLE, in contrast to a vesicular (Weibel-Palade body) cytoplasmic distribution in HUVE. The HUVE did demonstrate some extracellular fibrillar Factor VIII R-Ag as well. Urokinase was the predominant plasminogen activator (PA) secreted by HLE, whereas tissue PA was predominant in HUVE cultures. HLE formed tube-like structures within 2 h of plating on a Matrigel matrix whereas HUVE formed larger tube-like structures only after 1 or more days. The properties described here indicate that human lung microvessel endothelium can be isolated and continuously grown from small tissue segments and express a number of properties that differ from those of HUVE. These studies provide further support for the concept that endothelial cells from different sources can exhibit considerable heterogeneity relating to their phenotypic and biochemical properties.
Am J Respir Cell Mol Biol 1992 Dec
PMID:Isolation, cultivation, and partial characterization of microvascular endothelium derived from human lung. 133 46

The type of plasminogen activator (PA) secreted by bovine embryos was identified. Day 12-14 embryos were collected from estrus-synchronized, superovulated, and naturally mated crossbred beef cows. Embryos were left intact (E) or microdissected into component embryonic discs (ED) and trophoblastic vesicles (TV). Intact embryos, ED, and TV were pre-cultured for 2 days in Minimum Essential Medium Alpha (MEM alpha) with 10% heat-inactivated fetal calf serum, washed in serum-free MEM alpha, and cultured individually for 5 days in 50 microliters microdrops of MEM alpha with 15 mg/ml bovine serum albumin. At 24 hr intervals, E, ED, and TV were observed for tissue morphology and transferred to fresh microdrops, and medium was recovered and frozen at -20 degrees C. At the end of culture, blastocoelic fluid (BF) and embryonic tissues were recovered and frozen at -20 degrees C. Plasminogen activator concentrations in medium, tissues, and BF were determined by using a caseinolytic assay. Antibodies to urokinase-type PA (anti-uPA) and tissue-type PA (anti-tPA), and the urokinase inhibitor, amiloride (AMR), were used to identify the type of PA produced by bovine embryonic tissues. Intact embryos and TV released more PA (P less than 0.05) than ED, and tissues exhibiting expanded blastocoels released less PA (P less than 0.05) than tissues with collapsed blastocoels. Blastocoelic fluid from TV exhibited more PA (P less than 0.05) activity than from ED. Treatment with anti-uPA decreased PA activity (P less than 0.05) in pooled medium and tissues from E compared to treatment with nonspecific immunoglobulins and anti-tPA.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Reprod Dev 1992 Jan
PMID:Bovine embryos produce a urokinase-type plasminogen activator. 156 22

The surface receptor for urokinase plasminogen activator (uPAR) has been recognized in recent years as a key molecule in regulating plasminogen mediated extracellular proteolysis. Surface plasminogen activation controls the connections between cells, basement membrane and extracellular matrix, and therefore the capacity of cells to migrate and invade neighboring tissues. We have isolated a 1.4 kb cDNA clone coding for the entire human uPAR. An oligonucleotide synthesized on the basis of the N-terminal sequence of the purified protein was used to screen a cDNA library made from SV40 transformed human fibroblasts [Okayama and Berg (1983) Mol. Cell Biol., 3, 280-289]. The cDNA encodes a protein of 313 amino acids, preceded by a 21 residue signal peptide. A hydrophobicity plot suggests the presence of a membrane spanning domain close to the C-terminus. The cDNA hybridizes to a 1.4 kb mRNA from human cells, a size very close to that of the cloned cDNA. Expression of the uPAR cDNA in mouse cells confirms that the clone is complete and expresses a functional uPA binding protein, located on the cell surface and with properties similar to the human uPAR. Caseinolytic plaque assay, immunofluorescence analysis, direct binding studies and cross-linking experiments show that the transfected mouse LB6 cells specifically bind human uPA, which in turn activates plasminogen. The Mr of the mature human receptor expressed in mouse cells is approximately 55,000, in accordance with the naturally occurring, highly glycosylated human uPAR. The Mr calculated on the basis of the cDNA sequence, approximately 35,000, agrees well with that of the deglycosylated receptor.
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PMID:Cloning and expression of the receptor for human urokinase plasminogen activator, a central molecule in cell surface, plasmin dependent proteolysis. 168 40

Previous studies from our laboratory have demonstrated that OVCA 433 human ovarian carcinoma cells are glucocorticoid responsive by several criteria and contain high affinity, saturable, steroid-specific glucocorticoid receptors. These cells secrete both mammalian plasminogen activators (PAs), urokinase (uPA) and tissue-type PA (tPA). Treatment of OVCA 433 cells with 1 x 10(-7) M dexamethasone (Dex) for 4 days led to 77% and 83% reductions in the extracellular activities of uPA and tPA, respectively, released into serum-free conditioned medium during a 1-h period. Dex treatment led to a 71% decrease in the rate of extracellular uPA antigen accumulation, as determined by enzyme-linked immunosorbent assay, as well as a 73% reduction in steady state uPA mRNA levels. In contrast, Dex treatment led to only a 42% decrease in the rate of extracellular tPA antigen accumulation and a 48% decrease in tPA mRNA levels; such decreases were insufficient to account for the 83% reduction in tPA activity. Thus, while Dex-induced decreases in uPA antigen and mRNA levels accounted for all but 6% of the decrease in uPA activity, a large discrepancy existed between the magnitudes of decreased tPA activity and decreased tPA antigen and mRNA levels. OVCA 433 cells produce both PAI-1 and PAI-2, two specific PA inhibitors. Treatment of cells with 1 x 10(-7) M Dex for 4 days led to a 3.3-fold increase in the rate of extracellular PAI-1 accumulation, with little or no effect on PAI-2 accumulation.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Endocrinol 1989 Jun
PMID:Different mechanisms contribute to simultaneous inhibition of urokinase and tissue-type plasminogen activators by glucocorticoids in human ovarian carcinoma cells. 250 May 90

The secretion of plasminogen activator by seminiferous tubules at defined stages of the epithelial cycle is influenced both by neighboring spermatogenic cells and by hormones. We have used cRNA probes for urokinase-type (uPA) and tissue-type (tPA) plasminogen activators to analyze their mRNA levels in different stages of the epithelial cycle. Urokinase-type PA mRNA was most abundant in stages VII-VIII, while tPA mRNA levels showed smaller variations between the different stages. Both FSH and (Bu)2cAMP increased the steady-state level of tPA mRNA and tPA production without affecting those of uPA in stages VII-IX in vitro, whereas retinoic acid treatment selectively increased the concentration uPA mRNA and uPA production in stages II-VI. The results show that the expression of the uPA and tPA genes is differentially regulated in specific stages of the rat seminiferous epithelium.
Mol Endocrinol 1989 Jan
PMID:Regulation of urokinase- and tissue-type plasminogen activator gene expression in the rat seminiferous epithelium. 253 92

Human carcinoma HEp-3 lost its tumorigenic and metastatic potential upon prolonged culture in vitro. This change was accompanied by a reduced production of plasminogen activator (PA) of the urokinase type (uPA), which is secreted by HEp-3 cells, a change in response to effectors that modulate uPA production, and an alteration of cell morphology. Similar but more rapid changes occurred when malignant HEp-3 cells were exposed to dimethyl sulfoxide (DMSO). uPA activity in the culture medium dropped below 50% of the control level within 6 h after the addition of DMSO and became undetectable after 24 h of treatment. This drop in uPA activity was not caused by an increased production of PA inhibitors. The cell-associated uPA decreased to 25 to 30% of the control level within 6 h of DMSO treatment and remained at this level for at least 96 h; the reduced uPA production was partially accounted for by a rapid decrease in the functional and chemical concentration of uPA mRNA. In contrast, the concentrations of most of the abundant mRNA species did not appear to be significantly affected, and cell growth was only slightly inhibited in the presence of DMSO. Malignant HEp-3 cells treated with DMSO responded to cholera toxin with an enhanced production of uPA, and their morphology became indistinguishable from that of nonmalignant HEp-3 cells grown in vitro for prolonged periods of time. All of the above changes were fully and rapidly reversible. The inhibitory effect of DMSO on PA production appears to be specific for uPA of human cell lines.
Mol Cell Biol 1985 Dec
PMID:Effect of dimethyl sulfoxide on human carcinoma cells, inhibition of plasminogen activator synthesis, change in cell morphology, and alteration of response to cholera toxin. 383 48

Complex between urokinase and its type-1 inhibitor (uPA-PAI-1) may, when bound to the urokinase receptor (uPAR), be endocytosed by an ensuing binding of the complex to the multiligand receptors alpha (2)-macroglobulin receptor/low density lipoprotein receptor-related protein (alpha 2MR/LRP) and glycoprotein 330 (gp330). We have found that phorbol esters regulate endocytosis of uPA-PAI-1 differently in different cell lines. In COS-1 cells, expressing uPAR and high levels of alpha 2MR/LRP under basal conditions, phorbol esters cause a time-dependent decrease in endocytosis concomitantly with a parallel down-regulation of alpha 2MR/LRP expression. An up-regulation of uPAR expression was also observed. General endocytosis via the clathrin-coated pit pathway was not affected by PMA treatment, as judged from measurements of transferrin endocytosis. In LLC-PK1 cells, expressing alpha 2MR/LRP but not uPAR under basal conditions, phorbol esters transiently increase endocytosis in parallel with a transient induction of uPAR expression, while there was virtually no change in alpha 2MR/LRP expression. Differential regulation of endocytosis therefore seems to be caused by differential regulation of the receptors, with either the alpha 2MR/LRP-level (in COS)-1 cells) or the uPAR-level (in LLC-PK1 cells) being rate-limiting.
Mol Cell Endocrinol 1995 Apr 01
PMID:Differential regulation of urokinase-type-1 inhibitor complex endocytosis by phorbol esters in different cell lines is associated with differential regulation of alpha 2-macroglobulin receptor and urokinase receptor expression. 766 84

The expressions of urokinase (uPA) and tissue-type plasminogen activators (tPA) in different stages of the rat seminiferous epithelial cycle were analyzed by in situ and Northern hybridizations combined with zymographic analysis. Irradiated rat testes were used to assess the cell localization. Both of the plasminogen activators were expressed in a strictly stage specific manner. Maximal expression of uPA mRNA was seen in Sertoli cells during stages VII-VIII of the cycle. The same expression in the basal compartment of the tubules was detected at 7 days post-irradiation (p-i), during a selective reduction of spermatogonia and preleptotene spermatocytes. Levels of tPA mRNA started to accumulate in Sertoli cells at stage VIII and were high during stages IX-XII and detectable during stages XIII-XIV. At 26 days p-i, reduction of pachytene spermatocytes, which are shown to be immunoreactive for tPA, did not have an effect on tPA mRNA expression. Catalytic activities of uPA and tPA changed concomitantly to their RNA levels in different stages of the cycle. However, at 7 days p-i, uPA activity was decreased at stages VII-VIII of the cycle suggesting that germ cell Sertoli cell interaction is important for uPA activity.
Mol Cell Endocrinol 1994 Oct
PMID:Localization of urokinase- and tissue-type plasminogen activator mRNAs in rat testes. 782 18

Proteolytic enzymes are required to mediate tumor cell invasion of adjacent tissues and spread of primary tumors to distant sites. Our objective was to examine the activities and molecular forms of plasminogen activator (PA) and matrix metalloproteases (MP) in primary and secondary growths of SC tumors of three human prostatic cell lines (Du-145, PC-3, and 1-LN-PC-3-1A [1-LN], a subline of PC-3) grown in nude mice. The plasminogen activator activities were 1.7 +/- 1.3 (+/- SD), 6.2 +/- 2.8, and 11.5 +/- 4.2 for Du-145, PC-3, and 1-LN in primary SC tumors, respectively. Urokinase was the predominant molecular form of PA found in each tumor as determined from its molecular size (predominantly 54 kDa with a minor activity of 33 kDa) and sensitivity to amiloride. Prominent MP activities of approximately 68, 76, and 96 kDa as well as lesser activities of about 56, 59, 63, 84, 165, and 180 kDa were found in 1-LN tumors, whereas only less active MP of 59, 68, and 96 kDa were detected in the parental PC-3 cells. Du-145 tumors expressed MP activities of 59 and 96 kDa. Treatment of 1-LN tumor extracts with p-aminophenylmercuric acetate (APMA) significantly reduced the MP activities of 76 and 165 kDa while increasing activities of 56, 59, 65, 68, and 84 kDa. The 76 and 165 kDa MP activities thus appear to be prominent proenzyme forms of MP expressed in the 1-LN tumor. Secondary growths of tumor were subsequently found near the site of initial injection of PC-3 and 1-LN cells following removal of the primary tumor. There was a 42% increase in PA activity in the PC-3 secondary tumors, but only an 8% increase in 1-LN secondary tumors. However, there was no difference in the activities or number of molecular forms of MP in extracts of PC-3 or 1-LN primary or secondary tumors. The substantial expression of MP activities in the more aggressive 1-LN subline of the human prostatic PC-3 cell line indicates that induction of certain MP may be an important regulatory event in prostate tumor progression.
Cell Mol Biol Res 1993
PMID:Plasminogen activator and metalloprotease activities of Du-145, PC-3, and 1-LN-PC-3-1A human prostate tumors grown in nude mice: correlation with tumor invasive behavior. 795 14

Transcription factors which recognize both the SV40 promoter and the proximal promoter region of the human urokinase-type plasminogen activator (h-uPA) gene are present in nuclear extracts from primary cultures of mouse Sertoli cells; prolonged (more than 12 h) (Bu)2cAMP stimulation of Sertoli cells induces the formation of different specific DNA-protein complexes. A discrete region in the h-uPA promoter, between -54 and -42, is essential for the formation of the cAMP-induced DNA-protein complexes. Mutation of the sequence between -54 and -42 abolishes the response to cAMP of the proximal h-uPA promoter in Sertoli cells. A protein, recognizing a sequence centered around the GC-box present between -48 and -43, is detected by Southwestern analysis, and it is clearly induced by (Bu)2cAMP stimulation. Interaction between this protein and a second factor, recognizing a purine-rich sequence between -53 and -46, partially overlapping the GC-box, is needed for the formation of the cAMP-induced DNA-protein complexes. A preformed complex between the cAMP-induced GC-box-binding factor and the second factor can be detected using nondenaturing conditions during Southwestern analysis.
Mol Endocrinol 1993 Sep
PMID:Identification of 3',5'-cyclic adenosine monophosphate-inducible nuclear factors binding to the human urokinase promoter in mouse Sertoli cells. 824 23


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