Alpha 6 beta 4 signaling pathway (Bos taurus)

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CofilinAlpha 6 Beta 4 Signaling PathwaycytoskeletalRegulation of organisationITGB4LAMC1LAMB2LAMA2MAPK14PTPN11PRKCDSHC1SOS1HRASPIK3R2LAMC1LAMB2IRS1LAMA5ITGA6ITGA6AKT1RHOAITGA6MAPK1ITGB4ITGA6MTORLAMB1ITGB4LAMB1PIK3R1RAC1ITGB4LAMB3PRKCAMAPK3LAMA3LAMC1PTK2GRB2ITGA6ITGB4LAMA5LAMC1ITGA6LAMC2EIF4EBP1LAMB1ITGB4LAMC1LAMA2GAB1SRCLAMA1IRS2GTPPPPProtein - protein dissociationReceptorProteinEnzyme ComplexmRNAProteinProteinLigandSmall moleculeInduced activationInhibitionAuto catalysisTransportPositive regulation of gene expressionLeads to through unknown mechanismNegative regulation of gene expressionTranslocation UbiquitinationDeubiquitinationSumoylationInduced catalysisProtein-protein interactionAcetylationDephosphorylationLEGENDPhosphorylationDeacetylationGolgi apparatusEndosomeNucleusMitochondrionDesumoylationMethylationDemethylationPalmitoylationCytoplasmECPlasma membraneMTEndoplasmic reticulumCYPMGONUExtracellularERENProteolytic cleavageMolecule


Description

The integrin alpha6beta4 was discovered in the late 1980s by two different groups and was called either alphaEbeta4 or Ic-Ic binding protein (Ic-IcBP) (1,2). The alpha6beta4 integrin is a component of Hemidesmosomes (HDs) (3, 4,5). Increased expression of alphaEbeta4 and changes in its distribution is found to be correlated with increased aggressiveness of tumors and poor prognosis (6, 7). Although integrin alpha6beta4, can interact with different laminin isoforms, its preferred ligand in the epidermal BM is laminin-5 (8, 9). The beta4 integrin is a large protein and has a cytoplasmic domain of more than 1000 amino acids (10, 11). This domain contains a Na-Ca exchanger (CalX) motif followed by two pairs of type III fibronectin (FNIII) domains separated by a connecting segment (CS). It is found to associate with the intermediate filament system through plectin and BP230, which are components of hemidesmosomes (12,13,14). Interaction of intgrin beta4 with components of hemidesmosomes including plectin, BP230 and BP180 is found to be important in signaling events associated with cell growth, survival, and migration under physiological and pathological conditions.

Studies have shown that beta4 can regulate keratinocyte migration both positively and negatively (15,16,17,18). It is also found to regulate cell survival in keratinocytes in cell culture systems under stress in a PI3K/Akt pathway dependent manner (19,18). However, alpha6beta4 was not found to have any effect on keratinocyte survival in vivo (20, 18, 16). Apart from its effects on keratinocytes, evidence suggests that integrin alpha6beta4 is important in cancer cell invasion (21,22,23,24) and survival (25,26,27,28,16,29). The cancer cell invasion is regulated through a IRS/PI3K dependent process while the effect on carcinoma cell survival in a PI3K/Akt and dependent manner. Activation of the transcription factors NFkappaB and NF-IL6 in a p38Mapk dependent pathway and subsequent activation of IL6 gene expression was shown to be mechanism of alpha6beta4 induced survival of thymocytes and proliferation of thymic epithelial cells (27,30). Integrin alpha6beta4 is also known activate the Ras/Raf/MEK/ERK cascade which is found to be involved in the regulation of cell cycle (31,32,33,34).

NetPath (http://www.netpath.org) is a collaborative project between PandeyLab at Johns Hopkins University (http://pandeylab.igm.jhmi.edu) and the Institute of Bioinformatics (http://www.ibioinformatics.org). If you use this pathway, you must cite the NetPath website until the pathway is published.

Comments

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This pathway was inferred from Homo sapiens pathway WP244 with a 100% conversion rate.

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Bibliography

  1. Kandasamy K, Mohan SS, Raju R, Keerthikumar S, Kumar GS, Venugopal AK, Telikicherla D, Navarro JD, Mathivanan S, Pecquet C, Gollapudi SK, Tattikota SG, Mohan S, Padhukasahasram H, Subbannayya Y, Goel R, Jacob HK, Zhong J, Sekhar R, Nanjappa V, Balakrishnan L, Subbaiah R, Ramachandra YL, Rahiman BA, Prasad TS, Lin JX, Houtman JC, Desiderio S, Renauld JC, Constantinescu SN, Ohara O, Hirano T, Kubo M, Singh S, Khatri P, Draghici S, Bader GD, Sander C, Leonard WJ, Pandey A; ''NetPath: a public resource of curated signal transduction pathways.''; Genome Biol, 2010 PubMed Europe PMC Scholia

History

View all...
CompareRevisionActionTimeUserComment
117858view10:13, 23 May 2021EweitzModified title
115939view08:14, 21 March 2021EgonwCopied the NetPath paper into the literature list
115932view08:08, 21 March 2021EgonwModified description
85044view09:26, 10 April 2016EgonwReplaced a mim-conversion with mim-binding (protein-protein interaction).
80902view15:30, 30 June 2015Mkutmonhomology conversion
79846view07:19, 19 April 2015EgonwReplaced "Ensemble Cow" with "Ensembl".
79152view04:55, 6 March 2015MaintBotUpdated conversion from Hs
63396view00:04, 10 May 2013MaintBotUpdated to 2013 gpml schema
40569view19:32, 1 March 2011MaintBotRemoved redundant pathway information and comments
33807view00:19, 9 December 2009MaintBotAutomatic update of empty xrefs
31639view22:25, 13 August 2009MaintBotFixed text labels
30554view22:01, 29 July 2009MaintBotNew pathway

External references

DataNodes

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NameTypeDatabase referenceComment
AKT1Protein280991 (Entrez Gene)
EIF4EBP1Protein509613 (Entrez Gene)
GAB1Protein540085 (Entrez Gene)
GRB2ProteinENSBTAG00000004736 (Ensembl Cow)
HRASProtein100298939 (Entrez Gene)
IRS1Protein538598 (Entrez Gene)
IRS2Protein100300012 (Entrez Gene)
ITGA6Protein535043 (Entrez Gene) ITGB4 interacts with ITGA6 in PA-JEB keratinocytes, 804G cells,MDA-MB-435 cells and HUVECs.
ITGB4Protein506995 (Entrez Gene)
LAMA1Protein506387 (Entrez Gene)
LAMA2Protein100138434 (Entrez Gene)
LAMA3Protein100336873 (Entrez Gene)
LAMA5Protein506751 (Entrez Gene)
LAMB1Protein520030 (Entrez Gene)
LAMB2Protein520167 (Entrez Gene)
LAMB3Protein529939 (Entrez Gene)
LAMC1Protein532572 (Entrez Gene)
LAMC2Protein511043 (Entrez Gene)
MAPK1Protein327672 (Entrez Gene)
MAPK14Protein534492 (Entrez Gene)
MAPK3Protein531391 (Entrez Gene)
MTORProtein100139219 (Entrez Gene)
PIK3R1Protein282307 (Entrez Gene)
PIK3R2Protein282308 (Entrez Gene)
PRKCAProtein282001 (Entrez Gene)
PRKCDProtein505708 (Entrez Gene)
PTK2Protein506270 (Entrez Gene)
PTPN11Protein533590 (Entrez Gene)
RAC1Protein281440 (Entrez Gene)
RHOAProtein338049 (Entrez Gene)
SHC1Protein507196 (Entrez Gene)
SOS1ProteinENSBTAG00000011643 (Ensembl Cow)
SRCProtein535742 (Entrez Gene)

Annotated Interactions

No annotated interactions
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