Alpha 6 beta 4 signaling pathway (Homo sapiens)

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1cytoskeletalAlpha 6 beta 4 signaling pathwayRegulation of organisationCofilinIRS2PTPN11AKT1LAMC1ITGB4ITGB4LAMB2LAMC1EIF4EBP1LAMC2LAMC1LAMC1LAMC1SRCPRKCDLAMA5ITGA6MAPK14PIK3R1LAMA5ITGA6LAMB1LAMB3MTORLAMB1LAMB1PRKCAGAB1PIK3R2SHC1LAMB2ITGA6MAPK1PTK2LAMA2LAMA2ITGB4ITGB4ITGA6ITGA6LAMA3IRS1LAMA1HRASITGB4GRB2MAPK3RHOASOS1ITGA6RAC1ITGB4PGTPPPProtein - 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


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 ( is a collaborative project between PandeyLab at Johns Hopkins University ( and the Institute of Bioinformatics ( If you use this pathway, please cite the NetPath website until the pathway is published.

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  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


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120686view12:26, 23 December 2021EweitzStandardize font, weight, case
117645view11:42, 22 May 2021EweitzModified title
115920view16:59, 20 March 2021EgonwCopied the NetPath paper into the literature list
115915view14:44, 20 March 2021EgonwModified description
108319view20:44, 6 December 2019L DupuisConnected line
108318view20:44, 6 December 2019L DupuisConverted interactions to graphical lines in legend
85199view08:27, 25 April 2016EgonwReplaced a mim-conversion with Arrow.
78506view10:29, 7 January 2015MaintBotadded missing graphIds
72056view17:13, 24 October 2013Mkutmonupdated annotations for SOS1 and GRB2
71703view19:54, 17 October 2013MaintBotremoved data source from nodes without identifier
63141view19:17, 8 May 2013MaintBotUpdating GPML version
44947view12:32, 6 October 2011MartijnVanIerselOntology Term : 'integrin mediated signaling pathway' added !
44577view20:33, 20 September 2011MaintBotModified categories
44576view20:32, 20 September 2011MaintBot
44575view20:32, 20 September 2011MaintBotUpdating content to NetSlim
44117view20:47, 24 August 2011KhanspersReverted to version '23:41, 1 March 2011' by Khanspers
44044view23:33, 22 August 2011KhanspersModified description
44043view23:32, 22 August 2011KhanspersUpdating pathway from NetSlim
41155view23:41, 1 March 2011MaintBotRemoved redundant pathway information and comments
35307view00:07, 12 February 2010Nsalomonisconnected some lines
35298view23:12, 11 February 2010NsalomonisModified description
35283view22:44, 11 February 2010Nsalomonisin progress
35242view19:49, 11 February 2010NsalomonisModified description
21193view11:31, 14 November 2008MaintBot[[Pathway:Homo sapiens:Alpha6-Beta4-Integrin NetPath 1]] moved to [[Pathway:WP244]]: Moved to stable identifier
7896view13:46, 7 January 2008MaintBot[[Pathway:Human:Alpha6-Beta4-Integrin NetPath 1]] moved to [[Pathway:Homo sapiens:Alpha6-Beta4-Integrin NetPath 1]]: Renaming species
7573view16:00, 18 December 2007MaintBotfixed category names
7192view12:33, 4 November 2007MaintBotAdded categories to GPML
6896view12:04, 23 July 2007212.48.140.65
6293view22:17, 22 May 2007A.Pandeygpml file for [[Human:Alpha6-Beta4-Integrin_NetPath_1]]

External references


View all...
NameTypeDatabase referenceComment
AKT1Protein207 (Entrez Gene)
EIF4EBP1Protein1978 (Entrez Gene)
GAB1Protein2549 (Entrez Gene)
GRB2ProteinENSG00000177885 (Ensembl)
HRASProtein3265 (Entrez Gene)
IRS1Protein3667 (Entrez Gene)
IRS2Protein8660 (Entrez Gene)
ITGA6Protein3655 (Entrez Gene)
ITGB4Protein3691 (Entrez Gene)
LAMA1Protein284217 (Entrez Gene)
LAMA2Protein3908 (Entrez Gene)
LAMA3Protein3909 (Entrez Gene)
LAMA5Protein3911 (Entrez Gene)
LAMB1Protein3912 (Entrez Gene)
LAMB2Protein3913 (Entrez Gene)
LAMB3Protein3914 (Entrez Gene)
LAMC1Protein3915 (Entrez Gene)
LAMC2Protein3918 (Entrez Gene)
MAPK14Protein1432 (Entrez Gene)
MAPK1Protein5594 (Entrez Gene)
MAPK3Protein5595 (Entrez Gene)
MTORProtein2475 (Entrez Gene)
PIK3R1Protein5295 (Entrez Gene)
PIK3R2Protein5296 (Entrez Gene)
PRKCAProtein5578 (Entrez Gene)
PRKCDProtein5580 (Entrez Gene)
PTK2Protein5747 (Entrez Gene)
PTPN11Protein5781 (Entrez Gene)
RAC1Protein5879 (Entrez Gene)
RHOAProtein387 (Entrez Gene)
SHC1Protein6464 (Entrez Gene)
SOS1ProteinENSG00000115904 (Ensembl)
SRCProtein6714 (Entrez Gene)

Annotated Interactions

No annotated interactions

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