Alpha 6 beta 4 signaling pathway (WP244)

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, please cite the NetPath website until the pathway is published.
last edited

Authors

A.Pandey, 212.48.140.65, MaintBot, Nsalomonis, Khanspers, MartijnVanIersel, Mkutmon, Egonw, L Dupuis, and Eweitz

Cited In

Organism

Homo sapiens

Communities

Annotations

Pathway Ontology: integrin mediated signaling pathway

Participants

Label Type Compact Identifier
ITGB4 Protein ncbigene:3691
MAPK14 Protein ncbigene:1432
PTK2 Protein ncbigene:5747
ITGB4 Protein ncbigene:3691
MTOR Protein ncbigene:2475
MAPK1 Protein ncbigene:5594
IRS2 Protein ncbigene:8660
ITGA6 Protein ncbigene:3655
PRKCD Protein ncbigene:5580
MAPK3 Protein ncbigene:5595
GAB1 Protein ncbigene:2549
LAMA2 Protein ncbigene:3908
LAMB1 Protein ncbigene:3912
LAMA2 Protein ncbigene:3908
ITGA6 Protein ncbigene:3655
AKT1 Protein ncbigene:207
ITGB4 Protein ncbigene:3691
EIF4EBP1 Protein ncbigene:1978
LAMA5 Protein ncbigene:3911
LAMC1 Protein ncbigene:3915
PTPN11 Protein ncbigene:5781
LAMC2 Protein ncbigene:3918
PIK3R2 Protein ncbigene:5296
LAMB1 Protein ncbigene:3912
LAMC1 Protein ncbigene:3915
LAMA3 Protein ncbigene:3909
LAMB1 Protein ncbigene:3912
ITGB4 Protein ncbigene:3691
SOS1 Protein ensembl:ENSG00000115904
LAMB2 Protein ncbigene:3913
LAMB2 Protein ncbigene:3913
IRS1 Protein ncbigene:3667
ITGA6 Protein ncbigene:3655
GRB2 Protein ensembl:ENSG00000177885
RHOA Protein ncbigene:387
RAC1 Protein ncbigene:5879
LAMA1 Protein ncbigene:284217
LAMC1 Protein ncbigene:3915
LAMA5 Protein ncbigene:3911
ITGA6 Protein ncbigene:3655
ITGA6 Protein ncbigene:3655
SHC1 Protein ncbigene:6464
ITGB4 Protein ncbigene:3691
LAMC1 Protein ncbigene:3915
LAMC1 Protein ncbigene:3915
ITGA6 Protein ncbigene:3655
LAMB3 Protein ncbigene:3914
ITGB4 Protein ncbigene:3691
PIK3R1 Protein ncbigene:5295
SRC Protein ncbigene:6714
HRAS Protein ncbigene:3265
PRKCA Protein ncbigene:5578

References

  1. Kandasamy K, Mohan SS, Raju R, Keerthikumar S, Kumar GSS, Venugopal AK, et al. NetPath: a public resource of curated signal transduction pathways. Genome Biol. 2010 Jan 12;11(1):R3. PubMed Europe PMC Scholia