Macrophage-stimulating protein (MSP) signaling (Homo sapiens)

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24Osteoblast differentiationCell cycle regulationCell adhesion / motilityBlood brain barrierOther types of cancersCytokine secretion fromFVB and C57Bl6 miceperitoneal macrophagesBreast cancerDU145 & PC-3 cellsSuperoxideproductionCancer metastasisMolecular associationTGF-betapathway In adherent cells In T47D cellsPI3KDownregulationKidney fibrosis & Epithelial-mesenchymal transitionUpregulationLeads to phosphorylationRegulation of IFN-gamma signalingCell MigrationCytoplasmOsteoblastdifferentiationPhosphositeInhibitory effects onsystemic innate immunityCell proliferation, invasion & metastasisRegulation of tumor angiogenesisCYTransportRegulation ofnon-alcoholic steatohepatitisGenetically susceptibleMSP variant (p.R703C)to Crohn's disease andulcerative colitisCancer initiation, progression & EMTAnt-inflammatory responsein human monocytoid cellsNucleusEpithelial-mesenchymal transition Regulation of growth and apoptosis in RON+ Ba/F3 and MEL cellsRON OverexpressionCell motilityRegulation of hepatic gluconegenesisInhibition of anoikisRegulation of M1/M2 macrophage phenotypeCell ProliferationMDM Cellssf-RON overexpressionPreservation ofblood brain barrier integrityin intracerebral hemorrhagePI3K-dependentCell adhesionand motility Epithelial-mesenchymal transition Cell proliferation & anti-apoptosisCigarette smoke toxicityCell proliferation,migration,invasion & EMTCell proliferation & glucose metabolismMST19MAPK19Y187T185MST1R9Y1239Y1238MAPK39Y204T202SRCY4199PLCG19Y783AKT19S473T308MTORS24489RPS6KB1T4129PDCD49S457RPS6KA19T573RPS6S236S235S244S2409COL4A19ProteinmRNAReceptorNUProtein/ GeneProteinPCProtein/ GeneLigandMST11, 12, 22MST1R1, 12, 22PCNA12Y211ABL112P12AKT1P22MBD422Cancer MetastasisMST1R2MST12WNT10B2DEK2FZD12CTNNB12WNT10B2CTNNB12CYNUCLDN11MST18MST1R8sf-MST1R14SMAD2S46514S467SMAD3S42314S425PDPK114S241AKT1S473T30814ZEB114SLUG14SIP114CDH214CDH114RPS6KA38CDH18VIM8MST1R Δ 16523pYPTEN23S380MTORS244823AKT1S47323MAPK123Y187T185MAPK3Y204T20223MST1R18Prostate cancersf-MST1R16sf-RON overexpressionAKT116S473GSK3B16S9CTNNB116GLUT116LDHA16HK216Gastric cancerMST1R26RON overexpressionSMAD926S467S465SMAD5S465S46326SMAD1S463S46526ZEB226VIM26CDH126Endometrial cancerMST121MST1R21AKT1T30821S473MTOR21PRPS6KB1T41221S447T444JUNP21MAPK3P21MAPK121PRPS6KA421PTP53S4621S15S392RPS6KA5P21MesotheliomaMST119MST1R19MAPK119T185Y187MAPK319Y204T202SMAD1S46519S463SMAD519S463S465SMAD9S46719S465ALP19BGLAP19BSP19SP719 MST1 p.R703C27MST1R27AKT127S473MST14MST1R4IL104MMP94IL1B4MMP94IL1B4TNF4DifferentiatedU937 CellsMST129MST1R29PRKAA2T17224, 29P2429ACACA29PACO29CPT1A29PPARGC1A29MST120MST1R20PTK220AKT120SRC20MAPK320CYNUMAPK320MST130MST1R5MAPK15Y187T185MAPK3Y204T2025CDH15ACTA25RON overexpressionMST1R30NFKB130NFKB130TNF30IL1B30IL1030CYNUMST1R17RON overexpressionSRC17Y419SMAD2S465S46717SMAD3S425S42317MAPK1P17MAPK317PMAPK817PMAPK9P17MAPK14P17SMAD417IGF1R17FGFR117VEGFR117VEGFR217PDGFRA17PDGFRB17CDH217VIM17TGFB117ACTA217FN117CDH117MST113MST1R13STAT3Y70513STAT1P13MAPK113PMAPK313PMAPK8P13MAPK9P13MAPK14P13SOCS113SOCS313NR0B224MST125MST1R25PTK2Y39725MST1R11STAT3P11AKT1P11MAPK111PMAPK311PMAPK1411PEGR111FOS11NR4A111DUSP111DUSP611IL611CXCL211CXCL1011rh-MST110MST1R10PGAB1Y62710CTNNB110CTNNB110CYNUCLDN510OCLN10TJP110MST17 MST1RY13607Y1353MAPK17PMAPK87PPLCG17PPIK3R1P7SHC1P7GRB2P7PRKCB9S661 HSPB19S82RAF1S3389NDRG19T346ELK1S3839DUSP49MST1RY12399Y1238PIK3R19RAF19S338AKT19T308S473RPS6S236S235S240S2449MAPK1Y1879T185MAPK39T202Y204PIK3R19RONoverexpressionPDCD49In primary and metastatic tumorsand ER+ cells and HCC-1143 cellsMAPK1T1852Y187MAPK3Y204T2022ECCY12MAPK1T18512Y187MAPK312T202Y204CRKL12Y207PIK3CA22MST1R4NFKB118RELA18CXCL818CXCL518CXCL118VEGFA18NUSIX116CTNNB116CYNUMST1R16SRCY41910MAP2K120MAPK120MAPK120MAP2K220PARP1PC20Leads to through indirect/multiple reactionsIndirect regulation of expressionIndirect inhibitionProtein cleavagePI3KITGB125IL10CSF211CCL211CSF31111MST130In healthy smokeralveolar macrophagesand MDMsCytokine secretion in healthy smoker alveolar macrophages and MDMs IFNB1111Inflammation and innate immunityLigand other than MST1Direct regulation of expressionOvarian cancerPancreatic cancer


Description

A network map of Macrophage-stimulating protein (MSP) signaling

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Bibliography

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  1. Thobe MN, Gurusamy D, Pathrose P, Waltz SE; ''The Ron receptor tyrosine kinase positively regulates angiogenic chemokine production in prostate cancer cells.''; Oncogene, 2010 PubMed Europe PMC Scholia
  2. Wei X, Hao L, Ni S, Liu Q, Xu J, Correll PH; ''Altered exon usage in the juxtamembrane domain of mouse and human RON regulates receptor activity and signaling specificity.''; J Biol Chem, 2005 PubMed Europe PMC Scholia
  3. Santoro MM, Gaudino G, Villa-Moruzzi E; ''Protein phosphatase 1 binds to phospho-Ser-1394 of the macrophage-stimulating protein receptor.''; Biochem J, 2003 PubMed Europe PMC Scholia
  4. Moxley KM, Wang L, Welm AL, Bieniasz M; ''Short-form Ron is a novel determinant of ovarian cancer initiation and progression.''; Genes Cancer, 2016 PubMed Europe PMC Scholia
  5. Yu Q, Wang J, Li T, Xu X, Guo X, Ding S, Zhu L, Zou G, Chen Y, Zhang X; ''RON Mediates Tumor-Promoting Effects in Endometrial Adenocarcinoma.''; Biomed Res Int, 2021 PubMed Europe PMC Scholia
  6. Wang Z, Yang Y, Hu S, He J, Wu Z, Qi Z, Huang M, Liu R, Lin Y, Tan C, Xu M, Zhang Z; ''Short-form RON (sf-RON) enhances glucose metabolism to promote cell proliferation via activating β-catenin/SIX1 signaling pathway in gastric cancer.''; Cell Biol Toxicol, 2021 PubMed Europe PMC Scholia
  7. Zhang J, Sun L, Li W, Wang Y, Li X, Liu Y; ''Overexpression of macrophage stimulating 1 enhances the anti-tumor effects of IL-24 in esophageal cancer via inhibiting ERK-Mfn2 signaling-dependent mitophagy.''; Biomed Pharmacother, 2019 PubMed Europe PMC Scholia
  8. Danilkovitch A, Skeel A, Leonard EJ; ''Macrophage stimulating protein-induced epithelial cell adhesion is mediated by a PI3-K-dependent, but FAK-independent mechanism.''; Exp Cell Res, 1999 PubMed Europe PMC Scholia
  9. Privette Vinnedge LM, Benight NM, Wagh PK, Pease NA, Nashu MA, Serrano-Lopez J, Adams AK, Cancelas JA, Waltz SE, Wells SI; ''The DEK oncogene promotes cellular proliferation through paracrine Wnt signaling in Ron receptor-positive breast cancers.''; Oncogene, 2015 PubMed Europe PMC Scholia
  10. Chanda D, Li T, Song KH, Kim YH, Sim J, Lee CH, Chiang JY, Choi HS; ''Hepatocyte growth factor family negatively regulates hepatic gluconeogenesis via induction of orphan nuclear receptor small heterodimer partner in primary hepatocytes.''; J Biol Chem, 2009 PubMed Europe PMC Scholia
  11. Baird AM, Easty D, Jarzabek M, Shiels L, Soltermann A, Klebe S, Raeppel S, MacDonagh L, Wu C, Griggs K, Kirschner MB, Stanfill B, Nonaka D, Goparaju CM, Murer B, Fennell DA, O'Donnell DM, Barr MP, Mutti L, Reid G, Finn S, Cuffe S, Pass HI, Opitz I, Byrne AT, O'Byrne KJ, Gray SG; ''When RON MET TAM in Mesothelioma: All Druggable for One, and One Drug for All?''; Front Endocrinol (Lausanne), 2019 PubMed Europe PMC Scholia
  12. Lu T, Wang Z, Prativa S, Xu Y, Wang T, Zhang Y, Yu L, Xu N, Tang J, You W, Chen G, Zhang JH; ''Macrophage stimulating protein preserves blood brain barrier integrity after intracerebral hemorrhage through recepteur d'origine nantais dependent GAB1/Src/β-catenin pathway activation in a mouse model.''; J Neurochem, 2019 PubMed Europe PMC Scholia
  13. Côté M, Miller AD, Liu SL; ''Human RON receptor tyrosine kinase induces complete epithelial-to-mesenchymal transition but causes cellular senescence.''; Biochem Biophys Res Commun, 2007 PubMed Europe PMC Scholia
  14. Chanda D, Li J, Oligschlaeger Y, Jeurissen ML, Houben T, Walenbergh SM, Shiri-Sverdlov R, Neumann D; ''MSP is a negative regulator of inflammation and lipogenesis in ex vivo models of non-alcoholic steatohepatitis.''; Exp Mol Med, 2016 PubMed Europe PMC Scholia
  15. Kauder SE, Santell L, Mai E, Wright LY, Luis E, N'Diaye EN, Lutman J, Ratti N, Sa SM, Maun HR, Stefanich E, Gonzalez LC, Graham RR, Diehl L, Faubion WA Jr, Keir ME, Young J, Chaudhuri A, Lazarus RA, Egen JG; ''Functional consequences of the macrophage stimulating protein 689C inflammatory bowel disease risk allele.''; PLoS One, 2013 PubMed Europe PMC Scholia
  16. Iwama A, Yamaguchi N, Suda T; ''STK/RON receptor tyrosine kinase mediates both apoptotic and growth signals via the multifunctional docking site conserved among the HGF receptor family.''; EMBO J, 1996 PubMed Europe PMC Scholia
  17. Zhao H, Chen MS, Lo YH, Waltz SE, Wang J, Ho PC, Vasiliauskas J, Plattner R, Wang YL, Wang SC; ''The Ron receptor tyrosine kinase activates c-Abl to promote cell proliferation through tyrosine phosphorylation of PCNA in breast cancer.''; Oncogene, 2014 PubMed Europe PMC Scholia
  18. Ma Q, Guin S, Padhye SS, Zhou YQ, Zhang RW, Wang MH; ''Ribosomal protein S6 kinase (RSK)-2 as a central effector molecule in RON receptor tyrosine kinase mediated epithelial to mesenchymal transition induced by macrophage-stimulating protein.''; Mol Cancer, 2011 PubMed Europe PMC Scholia
  19. Danilkovitch A, Donley S, Skeel A, Leonard EJ; ''Two independent signaling pathways mediate the antiapoptotic action of macrophage-stimulating protein on epithelial cells.''; Mol Cell Biol, 2000 PubMed Europe PMC Scholia
  20. Wilson CB, Ray M, Lutz M, Sharda D, Xu J, Hankey PA; ''The RON receptor tyrosine kinase regulates IFN-gamma production and responses in innate immunity.''; J Immunol, 2008 PubMed Europe PMC Scholia
  21. Gunella G, Bardelli C, Amoruso A, Viano I, Balbo P, Brunelleschi S; ''Macrophage-stimulating protein differently affects human alveolar macrophages from smoker and non-smoker patients: evaluation of respiratory burst, cytokine release andNF-kappaB pathway.''; Br J Pharmacol, 2006 PubMed Europe PMC Scholia
  22. Jeong BC, Oh SH, Lee MN, Koh JT; ''Macrophage-Stimulating Protein Enhances Osteoblastic Differentiation via the Recepteur d'Origine Nantais Receptor and Extracellular Signal-Regulated Kinase Signaling Pathway.''; J Bone Metab, 2020 PubMed Europe PMC Scholia
  23. Park JS, Choi HI, Kim DH, Kim CS, Bae EH, Ma SK, Kim SW; ''RON Receptor Tyrosine Kinase Regulates Epithelial Mesenchymal Transition and the Expression of Pro-Fibrotic Markers via Src/Smad Signaling in HK-2 and NRK49F Cells.''; Int J Mol Sci, 2019 PubMed Europe PMC Scholia
  24. Chaudhuri A, Wilson NS, Yang B, Paler Martinez A, Liu J, Zhu C, Bricker N, Couto S, Modrusan Z, French D, Cupp J, Ashkenazi A; ''Host genetic background impacts modulation of the TLR4 pathway by RON in tissue-associated macrophages.''; Immunol Cell Biol, 2013 PubMed Europe PMC Scholia
  25. Ling Y, Kuang Y, Chen LL, Lao WF, Zhu YR, Wang LQ, Wang D; ''A novel RON splice variant lacking exon 2 activates the PI3K/AKT pathway via PTEN phosphorylation in colorectal carcinoma cells.''; Oncotarget, 2017 PubMed Europe PMC Scholia
  26. Tsutsui S, Noorbakhsh F, Sullivan A, Henderson AJ, Warren K, Toney-Earley K, Waltz SE, Power C; ''RON-regulated innate immunity is protective in an animal model of multiple sclerosis.''; Ann Neurol, 2005 PubMed Europe PMC Scholia
  27. Faham N, Zhao L, Welm AL; ''mTORC1 is a key mediator of RON-dependent breast cancer metastasis with therapeutic potential.''; NPJ Breast Cancer, 2018 PubMed Europe PMC Scholia
  28. Zhang K, Yao HP, Wang MH; ''Activation of RON differentially regulates claudin expression and localization: role of claudin-1 in RON-mediated epithelial cell motility.''; Carcinogenesis, 2008 PubMed Europe PMC Scholia
  29. Cunha S, Lin YC, Goossen EA, DeVette CI, Albertella MR, Thomson S, Mulvihill MJ, Welm AL; ''The RON receptor tyrosine kinase promotes metastasis by triggering MBD4-dependent DNA methylation reprogramming.''; Cell Rep, 2014 PubMed Europe PMC Scholia
  30. Ganesan R, Kolumam GA, Lin SJ, Xie MH, Santell L, Wu TD, Lazarus RA, Chaudhuri A, Kirchhofer D; ''Proteolytic activation of pro-macrophage-stimulating protein by hepsin.''; Mol Cancer Res, 2011 PubMed Europe PMC Scholia

History

View all...
CompareRevisionActionTimeUserComment
129512view15:21, 3 May 2024Ash iyerData nodes annotated - improper annotation ids
129458view01:01, 23 April 2024EweitzModified title
128417view13:53, 4 February 2024EweitzModified description
128416view13:29, 4 February 2024EweitzFix typo, tailor node dimensions to fit text, standardize case
128415view13:17, 4 February 2024EweitzModified title
127177view08:44, 9 August 2023EgonwMarked diseases as @Type="Other"
126207view10:20, 15 April 2023EgonwNot a mim-conversion
126206view23:35, 14 April 2023AlexanderPicoremoved xrefs with id="0"
126160view15:44, 11 April 2023Ash iyerOntology Term : 'ovarian disease' added !
126158view15:11, 11 April 2023Ash iyerOntology Term : 'cancer pathway' added !
126157view15:09, 11 April 2023Ash iyerOntology Term : 'breast cancer pathway' added !
126156view15:08, 11 April 2023Ash iyerConversion of datanodes to graphical elements
126155view15:02, 11 April 2023Ash iyerConversion of datanodes to grpahical elements
126151view14:49, 11 April 2023Ash iyerRe-annotation of nodes for missing cross-reference
126087view09:01, 4 April 2023Rex D A BNew pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
HSPB1Protein3315 (Entrez Gene)
IFNB1GeneProduct3456 (Entrez Gene)
MST1 p.R703CProteinNP_066278 (RefSeq)
MST1RProtein4486 (Entrez Gene)
ABL1Protein25 (Entrez Gene)
ACACAProtein31 (Entrez Gene)
ACOGeneProduct50681 (Entrez Gene)
ACTA2Protein59 (Entrez Gene)
AKT1Protein207 (Entrez Gene)
ALPGeneProduct11691 (Entrez Gene)
BGLAPGeneProduct12096 (Entrez Gene)
BSPGeneProduct103993 (Entrez Gene)
CCL2Protein20296 (Entrez Gene)
CDH1Protein999 (Entrez Gene)
CDH2Protein1000 (Entrez Gene)
CLDN1Protein9076 (Entrez Gene)
CLDN5Protein12741 (Entrez Gene)
COL4A1Protein1282 (Entrez Gene)
CPT1AGeneProduct12894 (Entrez Gene)
CRKLProtein1399 (Entrez Gene)
CSF2Protein12981 (Entrez Gene)
CSF3Protein12985 (Entrez Gene)
CTNNB1Protein12387 (Entrez Gene)
CTNNB1Protein1499 (Entrez Gene)
CXCL10Protein15945 (Entrez Gene)
CXCL1Protein2919 (Entrez Gene)
CXCL2Protein20310 (Entrez Gene)
CXCL5Protein6374 (Entrez Gene)
CXCL8Protein3576 (Entrez Gene)
DEKProtein110052 (Entrez Gene)
DUSP1Protein19252 (Entrez Gene)
DUSP4Protein1846 (Entrez Gene)
DUSP6Protein67603 (Entrez Gene)
EGR1Protein13653 (Entrez Gene)
ELK1Protein2002 (Entrez Gene)
Endometrial cancerOther
FGFR1Protein2260 (Entrez Gene)
FN1Protein2335 (Entrez Gene)
FOSProtein14281 (Entrez Gene)
FZD1Protein8321 (Entrez Gene)
GAB1Protein2549 (Entrez Gene)
GLUT1Protein6513 (Entrez Gene)
GRB2Protein2885 (Entrez Gene)
GSK3BProtein2932 (Entrez Gene)
Gastric cancerOther
HK2Protein3099 (Entrez Gene)
IGF1RProtein3480 (Entrez Gene)
IL10Protein16153 (Entrez Gene)
IL10Protein3586 (Entrez Gene)
IL1BProtein3553 (Entrez Gene)
IL6Protein16193 (Entrez Gene)
ITGB1Protein3688 (Entrez Gene)
JUNProtein3725 (Entrez Gene)
LDHAProtein3939 (Entrez Gene)
LigandProtein
Ligand other than MST1Protein7480 (Entrez Gene)
MAP2K1Protein5604 (Entrez Gene)
MAP2K2Protein5605 (Entrez Gene)
MAPK14Protein1432 (Entrez Gene)
MAPK1Protein5594 (Entrez Gene)
MAPK3Protein5595 (Entrez Gene)
MAPK8Protein5599 (Entrez Gene)
MAPK9Protein5601 (Entrez Gene)
MBD4Protein4486 (Entrez Gene)
MMP9GeneProduct4318 (Entrez Gene)
MST1Protein4485 (Entrez Gene)
MST1R Δ 165Protein4486 (Entrez Gene)
MST1RProtein4486 (Entrez Gene)
MTORProtein2475 (Entrez Gene)
MesotheliomaOther
NDRG1Protein10397 (Entrez Gene)
NFKB1Protein4790 (Entrez Gene)
NR0B2Protein23957 (Entrez Gene)
NR4A1Protein15370 (Entrez Gene)
OCLNProtein18260 (Entrez Gene)
PARP1Protein142 (Entrez Gene)
PCNAProtein5111 (Entrez Gene)
PDCD4Protein27250 (Entrez Gene)
PDGFRAProtein5156 (Entrez Gene)
PDGFRBProtein5159 (Entrez Gene)
PDPK1Protein5170 (Entrez Gene)
PIK3CAProtein207 (Entrez Gene)
PIK3R1Protein5295 (Entrez Gene)
PLCG1Protein5335 (Entrez Gene)
PPARGC1AGeneProduct19017 (Entrez Gene)
PRKAA2Protein5563 (Entrez Gene)
PRKCBProtein5579 (Entrez Gene)
PTENProtein5728 (Entrez Gene)
PTK2Protein5747 (Entrez Gene)
Pancreatic cancerOther
Prostate cancerOther
ProteinProtein
Protein/ GeneProtein
RAF1Protein5894 (Entrez Gene)
RELAProtein5970 (Entrez Gene)
RPS6Protein6194 (Entrez Gene)
RPS6KA1Protein6195 (Entrez Gene)
RPS6KA3Protein6197 (Entrez Gene)
RPS6KA4Protein8986 (Entrez Gene)
RPS6KA5Protein9252 (Entrez Gene)
RPS6KB1Protein6198 (Entrez Gene)
ReceptorOther
SHC1Protein6464 (Entrez Gene)
SIP1GeneProduct9839 (Entrez Gene)
SIX1Protein6495 (Entrez Gene)
SLUGGeneProduct20583 (Entrez Gene)
SMAD1Protein17125 (Entrez Gene)
SMAD1Protein4086 (Entrez Gene)
SMAD2Protein4087 (Entrez Gene)
SMAD3Protein4088 (Entrez Gene)
SMAD4Protein4091 (Entrez Gene)
SMAD5Protein17129 (Entrez Gene)
SMAD5Protein4090 (Entrez Gene)
SMAD9Protein4093 (Entrez Gene)
SMAD9Protein55994 (Entrez Gene)
SOCS1Protein12703 (Entrez Gene)
SOCS3Protein12702 (Entrez Gene)
SP7GeneProduct170574 (Entrez Gene)
SRCProtein6714 (Entrez Gene)
STAT1Protein17125 (Entrez Gene)
STAT3Protein20848 (Entrez Gene)
STAT3Protein4088 (Entrez Gene)
TGFB1Protein7040 (Entrez Gene)
TJP1Protein21872 (Entrez Gene)
TNFProtein7124 (Entrez Gene)
TP53Protein7157 (Entrez Gene)
VEGFAGeneProduct7422 (Entrez Gene)
VEGFR1Protein2321 (Entrez Gene)
VEGFR2Protein3791 (Entrez Gene)
VIMProtein7431 (Entrez Gene)
WNT10BProtein7480 (Entrez Gene)
ZEB1GeneProduct21417 (Entrez Gene)
ZEB2Protein9839 (Entrez Gene)
mRNARna
rh-MST1GeneProduct4485 (Entrez Gene)
sf-MST1RProtein4486 (Entrez Gene)

Annotated Interactions

No annotated interactions

Retrieved from "https://classic.wikipathways.org/index.php/Pathway:WP5353"