Alpha 6 beta 4 signaling pathway (WP985)

Bos taurus

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.

Authors

Egon Willighagen , Martina Summer-Kutmon , and Eric Weitz

Activity

last edited

Discuss this pathway

Check for ongoing discussions or start your own.

Cited In

Are you planning to include this pathway in your next publication? See How to Cite and add a link here to your paper once it's online.

Organisms

Bos taurus

Communities

Annotations

Pathway Ontology

integrin mediated signaling pathway

Participants

Label Type Compact URI Comment
ITGB4 Protein ensembl:ENSBTAG00000018169 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3691
MAPK14 Protein ensembl:ENSBTAG00000020783 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:1432
PTK2 Protein ensembl:ENSBTAG00000009578 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5747
MTOR Protein ensembl:ENSBTAG00000015325 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:2475
MAPK1 Protein ensembl:ENSBTAG00000010312 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5594
IRS2 Protein ensembl:ENSBTAG00000012019 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:8660
ITGA6 Protein ensembl:ENSBTAG00000017266 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3655
PRKCD Protein ensembl:ENSBTAG00000008719 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5580
MAPK3 Protein ensembl:ENSBTAG00000016156 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5595
GAB1 Protein ensembl:ENSBTAG00000002813 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:2549
LAMA2 Protein ensembl:ENSBTAG00000010229 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3908
LAMB1 Protein ensembl:ENSBTAG00000011412 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3912
AKT1 Protein ensembl:ENSBTAG00000017636 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:207
EIF4EBP1 Protein ensembl:ENSBTAG00000027654 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:1978
LAMA5 Protein ensembl:ENSBTAG00000003061 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3911
LAMC1 Protein ensembl:ENSBTAG00000011966 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3915
PTPN11 Protein ensembl:ENSBTAG00000002048 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5781
LAMC2 Protein ensembl:ENSBTAG00000000793 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3918
LAMA3 Protein ensembl:ENSBTAG00000027181 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3909
SOS1 Protein ensembl:ENSBTAG00000011643 HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000115904
LAMC1 Protein ensembl:ENSBTAG00000022635 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3913
IRS1 Protein ensembl:ENSBTAG00000021308 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3667
GRB2 Protein ensembl:ENSBTAG00000004736 HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000177885
RHOA Protein ensembl:ENSBTAG00000004279 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:387
RAC1 Protein ensembl:ENSBTAG00000009233 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5879
LAMA1 Protein ensembl:ENSBTAG00000018160 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:284217
ITGA6 Protein ensembl:ENSBTAG00000017266 ITGB4 interacts with ITGA6 in PA-JEB keratinocytes, 804G cells,MDA-MB-435 cells and HUVECs.
HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3655
SHC1 Protein ensembl:ENSBTAG00000019838 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6464
LAMB3 Protein ensembl:ENSBTAG00000016542 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3914
PIK3R1 Protein ensembl:ENSBTAG00000010989 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5295
SRC Protein ensembl:ENSBTAG00000008938 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6714
HRAS Protein ensembl:ENSBTAG00000046644 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3265
PRKCA Protein ensembl:ENSBTAG00000001061 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5578

References

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