loading...| Preferred Name |
Peutz-Jeghers Syndrome |
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| Synonyms |
PMID: 19916169 PathwayType: signaling Description: Peutz-Jeghers syndrome (PJS) is a rare autosomal dominant inherited disorder, is characterized by mucocutaneous pigmentations, gastrointestinal polyposis, and an increased risk of cancers. Pathway is built manually using published studies. Organ: pancreas CellType: epithelial cell Notes: Headnote: Peutz-Jeghers syndrome (PJS) is a rare autosomal dominant inherited disorder which is characterized by mucocutaneous pigmentations, gastrointestinal polyposis, and an increased risk of cancers. PJS is caused by germline mutations in STK11 tumor suppressor gene which results in the development of hamartomatous polyps at an early age which may cause various complications including abdominal pain, anemia, and acute intestinal obstruction. In addition, patients have an increased risk of developing various cancers including gastrointestinal, pancreatic, lung, breast, uterine, ovarian, and testicular. The pathogenesis of hamartomas and carcinomas is unclear. Signaling description: STK11 is a master kinase involved in the regulation of multiple signaling pathways. STK11 forms a heterotrimeric complex with psuedokinase STRADA and scaffold protein CAB39. These proteins regulate STK11 stability, kinase activity, and subcellular localization. The physiological function of this protein complex is to regulate multiple biological pathways involving TP53-dependent and independent apoptosis, cell cycle and proliferation, chromatin remodeling, angiogenesis, energy metabolism, and control of cell polarity. Normally, STK11 phosphorylates and activates PTEN, AMPK, TP53, and SMAD4. PTEN negatively regulates intracellular levels of PIP3 and functions as a tumor suppressor by negatively regulating AKT1 signaling pathway. AMPK is a heterotrimer consisting of an alpha catalytic subunit (PRKAA1), two non-catalytic beta (PRKAB1), and gamma (PRKAG1) subunits. AMPK is an important energy-sensing enzyme that monitors cellular energy status. Outcome effects: Activated AKT1 phosphorylates and activates MTOR which is a central regulator of cellular glucose and lipid metabolism, growth, and survival. In addition, AKT1 inhibits FOXO1 and FOXO3 which are involved in cell differentiation and apoptosis. AKT1 directly phosphorylates TSC1 and TSC2 to inactivate TSC1/2 tumor suppressor complex. TSC1/2 complex inactivates the small GTPase RHEB which activates MTOR via RPTOR. TSC2 interacts with SMAD2 and SMAD3 which bind to SMAD4 and forms a heterotrimeric complex. This complex then enters the cell nucleus where it acts as a transcription factor for various genes involved in cell functions. At the same time, activated AMPK stimulates TSC1/2 complex, through AMPK-mediated TSC2 phosphorylation, and thus inhibits MTOR signaling. Further, STK11 suppresses tumor growth by inhibiting STAT3 which acts as a transcription activator and plays a key role in many cellular processes such as cell proliferation, differentiation, cell cycle, apoptosis, and vascularization. STK11 interacts with SMARCA4, an essential component of chromatin remodeling complex. Germline mutations of STK11 lead to disruption of cell cycle, differentiation, and metabolism in addition to redundant cell proliferation, block of apoptosis, and chromatin remodeling which result in tumorigenesis. Mutated genes: Mutated gene is shown in white-out style. Tissue: epithelium Organ_System: reproductive system NodeType: Pathway Organ_System: digestive system Link: https://mammal-profservices.pathwaystudio.com/app/sd?urn=urn:agi-pathway:uuid-f1a35eca-5871-4446-9029-c42475ab0e8e Organ_System: integumentary system PMID: 23287572 Pathway_Author: M. Zharkova ORCID:0000-0001-8706-9411 Source: Diseases PMID: 21272562 |
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| ID |
urn:agi-pathway:uuid-f1a35eca-5871-4446-9029-c42475ab0e8e |
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| database_cross_reference |
PS:PathwayType PS:Description PS:Tissue PS:Pathway_Author PS:Link PS:CellType PS:Organ_System PS:PMID PS:NodeType PS:Notes PS:Organ PS:Source |
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| has_exact_synonym |
PMID: 19916169 PathwayType: signaling Description: Peutz-Jeghers syndrome (PJS) is a rare autosomal dominant inherited disorder, is characterized by mucocutaneous pigmentations, gastrointestinal polyposis, and an increased risk of cancers. Pathway is built manually using published studies. Organ: pancreas CellType: epithelial cell Notes: Headnote: Peutz-Jeghers syndrome (PJS) is a rare autosomal dominant inherited disorder which is characterized by mucocutaneous pigmentations, gastrointestinal polyposis, and an increased risk of cancers. PJS is caused by germline mutations in STK11 tumor suppressor gene which results in the development of hamartomatous polyps at an early age which may cause various complications including abdominal pain, anemia, and acute intestinal obstruction. In addition, patients have an increased risk of developing various cancers including gastrointestinal, pancreatic, lung, breast, uterine, ovarian, and testicular. The pathogenesis of hamartomas and carcinomas is unclear. Signaling description: STK11 is a master kinase involved in the regulation of multiple signaling pathways. STK11 forms a heterotrimeric complex with psuedokinase STRADA and scaffold protein CAB39. These proteins regulate STK11 stability, kinase activity, and subcellular localization. The physiological function of this protein complex is to regulate multiple biological pathways involving TP53-dependent and independent apoptosis, cell cycle and proliferation, chromatin remodeling, angiogenesis, energy metabolism, and control of cell polarity. Normally, STK11 phosphorylates and activates PTEN, AMPK, TP53, and SMAD4. PTEN negatively regulates intracellular levels of PIP3 and functions as a tumor suppressor by negatively regulating AKT1 signaling pathway. AMPK is a heterotrimer consisting of an alpha catalytic subunit (PRKAA1), two non-catalytic beta (PRKAB1), and gamma (PRKAG1) subunits. AMPK is an important energy-sensing enzyme that monitors cellular energy status. Outcome effects: Activated AKT1 phosphorylates and activates MTOR which is a central regulator of cellular glucose and lipid metabolism, growth, and survival. In addition, AKT1 inhibits FOXO1 and FOXO3 which are involved in cell differentiation and apoptosis. AKT1 directly phosphorylates TSC1 and TSC2 to inactivate TSC1/2 tumor suppressor complex. TSC1/2 complex inactivates the small GTPase RHEB which activates MTOR via RPTOR. TSC2 interacts with SMAD2 and SMAD3 which bind to SMAD4 and forms a heterotrimeric complex. This complex then enters the cell nucleus where it acts as a transcription factor for various genes involved in cell functions. At the same time, activated AMPK stimulates TSC1/2 complex, through AMPK-mediated TSC2 phosphorylation, and thus inhibits MTOR signaling. Further, STK11 suppresses tumor growth by inhibiting STAT3 which acts as a transcription activator and plays a key role in many cellular processes such as cell proliferation, differentiation, cell cycle, apoptosis, and vascularization. STK11 interacts with SMARCA4, an essential component of chromatin remodeling complex. Germline mutations of STK11 lead to disruption of cell cycle, differentiation, and metabolism in addition to redundant cell proliferation, block of apoptosis, and chromatin remodeling which result in tumorigenesis. Mutated genes: Mutated gene is shown in white-out style. Tissue: epithelium Organ_System: reproductive system NodeType: Pathway Organ_System: digestive system Organ_System: integumentary system PMID: 23287572 Pathway_Author: M. Zharkova ORCID:0000-0001-8706-9411 Source: Diseases PMID: 21272562 |
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| id |
urn:agi-pathway:uuid-f1a35eca-5871-4446-9029-c42475ab0e8e |
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| label |
Peutz-Jeghers Syndrome |
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| notation |
uuid-f1a35eca-5871-4446-9029-c42475ab0e8e |
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| prefLabel |
Peutz-Jeghers Syndrome |
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| treeView |
urn:agi-folder:reproductive_system urn:agi-folder:digestive_system urn:agi-folder:peutz-jeghers_syndrome urn:agi-folder:p urn:agi-folder:epithelium urn:agi-folder:integumentary_system |
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| subClassOf |
urn:agi-folder:reproductive_system urn:agi-folder:digestive_system urn:agi-folder:peutz-jeghers_syndrome urn:agi-folder:p urn:agi-folder:epithelium urn:agi-folder:integumentary_system |