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

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15Breast CancerDU145 & PC-3 cellsSuperoxideproductionCytokine secretion fromFVB and C57Bl6 miceperitoneal macrophagesCancer 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 of Non-alcoholic steatohepatitisGenetically susceptibleMSP variant (p.R703C)to Crohn's disease andulcerative colitisCancer Initiation, Progression & EMTAnt-inflammatory responesin human monocytoid cellsNucleus Epithelial-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 metabolismMST13MAPK13Y187T185MST1RY12383Y1239MAPK3Y204T2023SRCY4193PLCG1Y7833AKT1T308S4733MTORS24483RPS6KB1T4123PDCD43S457RPS6KA13T573RPS63S235S236S244S240COL4A13ProteinmRNAReceptorNUProtein/ GeneProteinPCProtein/ GeneLigandMST16, 7, 28MST1R6, 7, 28PCNA6Y211ABL1P66AKT17PMBD47Cancer MetastasisMST1R16MST116WNT10B16DEK16FZD116CTNNB116WNT10B16CTNNB116CYNUCLDN128MST126MST1R26sf-MST1R19SMAD219S467S465SMAD3S423S42519PDPK1S24119AKT119T308S473ZEB119SLUG19SIP119CDH219CDH119RPS6KA326CDH126VIM26MST1R Δ 165pY8PTEN8S380MTOR8S2448AKT18S473MAPK1Y187T1858MAPK3T2028Y204MST1R17Prostate Cancersf-MST1R18sf-RON OverexpressionAKT1S47318GSK3B18S9CTNNB118GLUT118LDHA18HK218Gastric CancerMST1R29RON OverexpressionSMAD929S465S467SMAD5S46329S465SMAD1S46329S465ZEB229VIM29CDH129Endometrial CancerMST125MST1R25AKT1S47325T308MTOR25PRPS6KB1T41225S447T444JUN25PMAPK325PMAPK1P25RPS6KA425PTP5325S46S392S15RPS6KA5P25MesotheliomaOther Types Of CancersMST114MST1R14MAPK114Y187T185MAPK314T202Y204SMAD114S463S465SMAD5S463S46514SMAD914S467S465ALP14BGLAP14BSP14SP714 MST1 p.R703C13MST1R13AKT1S47313MST111MST1R11IL1011MMP911IL1B11MMP911IL1B11TNF11DifferentiatedU937 CellsMST15MST1R5PRKAA25, 15T172P515ACACA5PACO5CPT1A5PPARGC1A5MST14MST1R4PTK24AKT14SRC4MAPK34CYNUMAPK34MST124MST1R12MAPK1T185Y18712MAPK312T202Y204CDH112ACTA212RON OverexpressionMST1R24NFKB124NFKB124TNF24IL1B24IL1024CYNUMST1R1RON overexpressionSRCY4191SMAD2S4671S465SMAD31S425S423MAPK11PMAPK31PMAPK81PMAPK91PMAPK141PSMAD41IGF1R1FGFR11VEGFR11VEGFR21PDGFRA1PDGFRB1CDH21VIM1TGFB11ACTA21FN11CDH11MST130MST1R30STAT3Y70530STAT1P30MAPK1P30MAPK3P30MAPK830PMAPK9P30MAPK14P30SOCS130SOCS330NR0B215MST19MST1R9PTK2Y3979MST1R23STAT3P23AKT1P23MAPK1P23MAPK323PMAPK1423PEGR123FOS23NR4A123DUSP123DUSP623IL623CXCL223CXCL1023rh-MST12MST1RP2GAB12Y627CTNNB12CTNNB12CYNUCLDN52OCLN2TJP12MST127 MST1RY135327Y1360MAPK1P27MAPK827PPLCG1P27PIK3R127PSHC1P27GRB2P27PRKCB3S661 HSPB13S82RAF13S338NDRG1T3463ELK13S383DUSP43MST1RY1238Y12393PIK3R13RAF1S3383AKT1T3083S473RPS6S235S244S2363S240MAPK1T1853Y187MAPK33T202Y204PIK3R13RONOverexpressionPDCD43In primary and metastatic tumorsand ER+ cells and HCC-1143 cellsMAPK1Y18716T185MAPK3T20216Y204ECCY6MAPK1Y187T1856MAPK3T2026Y204CRKL6Y207PIK3CA7MST1R11 Cell Cycle RegulationNFKB117RELA17CXCL817CXCL517CXCL117VEGFA17NUSIX118CTNNB118CYNUMST1R18SRC2Y419MAP2K14MAPK14MAPK14MAP2K24PARP1PC4Leads to through indirect/multiple reactionsIndirect regulation of gene / protein expressionIndirect inhibitionProtein CleavagePI3KITGB19IL1023CSF223CCL223CSF323MST124In healthy smokeralveolar macrophagesand MDMsCytokine secretion in healthy smoker alveolar macrophages and MDMs IFNB12328Inflammation and Innate immunityLigand other than MST1Direct regulation of gene / protein expression Cell adhesion/motilityBlood Brain BarrierOsteoblastDifferentiationOvarian 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
Cell Cycle RegulationGeneProduct0 (Entrez Gene)
Cell adhesion/motilityGeneProduct0 (Entrez Gene)
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)
Blood Brain BarrierGeneProduct0 (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 CancerGeneProduct0 (Entrez Gene)
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 CancerGeneProduct0 (Entrez Gene)
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)
Ligand other than MST1Protein7480 (Entrez Gene)
LigandProtein0 (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)
MesotheliomaGeneProduct0 (Entrez Gene)
NDRG1Protein10397 (Entrez Gene)
NFKB1Protein4790 (Entrez Gene)
NR0B2Protein23957 (Entrez Gene)
NR4A1Protein15370 (Entrez Gene)
OCLNProtein18260 (Entrez Gene)
Osteoblast DifferentiationGeneProduct0 (Entrez Gene)
Other Types Of CancersGeneProduct0 (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 CancerGeneProduct0 (Entrez Gene)
Prostate CancerGeneProduct0 (Entrez Gene)
Protein/ GeneProtein0 (Entrez Gene)
ProteinProtein0 (Entrez Gene)
RAF1Protein5894 (Entrez Gene)
RELAProtein5970 (Entrez Gene)
RPS6Protein6194 (Entrez Gene)
RPS6KA1Protein6195 (Entrez Gene)
RPS6KA3Protein6197 (Entrez Gene)
RPS6KA4Protein8986 (Entrez Gene)
RPS6KA5Protein9252 (Entrez Gene)
RPS6KB1Protein6198 (Entrez Gene)
Receptor0 (Entrez Gene)
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)
mRNARna0 (Entrez Gene)
rh-MST1GeneProduct4485 (Entrez Gene)
sf-MST1RProtein4486 (Entrez Gene)

Annotated Interactions

No annotated interactions

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