Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.73 (urokinase-type plasminogen activator)
 10,685 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

One of cAMP-regulatory sites in the porcine urokinase-type plasminogen activator (uPA) gene resides 3.4 kb upstream of the transcription initiation site and is composed of three protein binding domains, FPA, FPB and FPC. Whereas FPA and FPB contain a CRE-like sequence, the FPC sequence is not related to any known protein recognition sequences, yet all three domains are required to mediate cAMP action on a heterologous promoter. To study the functional cooperation among these three domains we purified and cloned a FPC-binding protein (FPCB) from porcine kidney derived LLC-PK1 cells. Sequence comparisons showed that FPCB is homologous to mouse LFB3 and rat vHNF1. LFB3/vHNF1 is related to a liver specific transcription factor HNF1, it recognizes the same sequence as HNF1 and is highly expressed in kidney cells. FPCB and HNF1 recognition sequences are dissimilar, nevertheless both sequences are recognized by in vitro-translated LFB3 and FPCB, indicating that binding to the two different sequences is an intrinsic character of FPCB/LFB3/vHNF1. In HeLa cells, this cAMP-responsive site was inactive whether FPCB was overexpressed or not, suggesting a requirement for an additional cell-specific factor. These results may suggest a mechanism by which hormonal control is integrated into cell-specific gene regulation.
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PMID:Purification and cDNA cloning of a transcription factor which functionally cooperates within a cAMP regulatory unit in the porcine uPA gene. 838 98

A cyclic AMP (cAMP)-inducible enhancer in the pig urokinase-type plasminogen activator gene located 3.4 kb upstream of the transcription initiation site is composed of three protein-binding domains, A, B, and C. Domains A and B each contain a CRE (cAMP response element)-like sequence but require the adjoining C domain for full cAMP responsiveness. A tissue-specific transcription factor, LFB3/HNF1beta/vHNF1, binds to the C domain. Mutation analyses suggest that the imperfect CRE and LFB3-binding sequences are required for tight coupling of hormonal and tissue-specific regulation. CREB and ATF1 bind to domains A and B, and this binding is enhanced upon phosphorylation by cAMP-dependent protein kinase (protein kinase A [PKA]). Analysis in a mammalian two-hybrid system revealed that CREB/ATF1 and LFB3 interact and that transactivation potential is enhanced by PKA activation. Interestingly, however, phosphorylation of CREB at Ser-133 does not contribute to its interaction with LFB3. The region of LFB3 involved in its interaction with CREB/ATF1 lies, at least partly, between amino acids 400 and 450. Deletion of this region removed the ability of LFB3 to mediate cAMP induction of the ABC enhancer but did not impair its basal transactivation activity on the albumin promoter. Thus, the two activities are distinct functions of LFB3.
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PMID:Role of tissue-specific transcription factor LFB3 in a cyclic AMP-responsive enhancer of the urokinase-type plasminogen activator gene in LLC-PK1 cells. 967 80