CDB15:0000013 ADAM17 — ITGB1

Experimentally validated in Human, Mouse; Orthology-inferred in Human, Rat, Frog, Zebrafish, Chicken, Macaque, Pig, Dog, Cow, Chimp, Horse, Marmoset, Sheep, Mouse

Title

Journal:; Year Published:

Abstract

Integrin alpha5beta1 and ADAM-17 interact in vitro and co-localize in migrating HeLa cells.

The Journal of biological chemistry, 2004; PubMed, Homo sapiens ADAM17 — Homo sapiens ITGB1

ABSTRACT: Tumor necrosis factor (TNF) alpha-converting enzyme (TACE/ADAM-17) has diverse roles in the proteolytic processing of cell surface molecules and, due to its ability to process TNFalpha, is a validated therapeutic target for anti-inflammatory therapies. Unlike a number of other ADAM proteins, which interact with integrin receptors via their disintegrin domains, there is currently no evidence for an ADAM-17-integrin association. By analyzing the adhesion of a series of cell lines with recombinant fragments of the extracellular domain of ADAM-17, we now demonstrate a functional interaction between ADAM-17 and alpha(5)beta(1) integrin in a trans orientation. Because ADAM-17-mediated adhesion was sensitive to RGD peptides and EDTA, and the integrin-binding site within ADAM-17 was narrowed down to the disintegrin/cysteine-rich region, the two molecules appear to have a ligand-receptor relationship mediated by the alpha(5)beta(1) ligand binding pocket. Intriguingly, ADAM-17 and alpha(5)beta(1) were found to co-localize in both membrane ruffles and focal adhesions in HeLa cells. When confluent HeLa cell monolayers were wounded, ADAM-17 and alpha(5)beta(1) redistributed to the leading edge and co-localized, which is suggestive of a cis orientation. We postulate that the interaction of ADAM-17 with alpha(5)beta(1) may target or modulate its metalloproteolytic activity.

Strain-induced differentiation of fetal type II epithelial cells is mediated via the integrin α6β1-ADAM17/tumor necrosis factor-α-converting enzyme (TACE) signaling pathway.

The Journal of biological chemistry, 2013; PubMed, Mus Musculus Adam17 — Mus Musculus Itgb1

ABSTRACT: Mechanical forces are critical for normal fetal lung development. However, the mechanisms regulating this process are not well-characterized. We hypothesized that strain-induced release of HB-EGF and TGF-α is mediated via integrin-ADAM17/TACE interactions. Employing an in vitro system to simulate mechanical forces in fetal lung development, we showed that mechanical strain of fetal epithelial cells actives TACE, releases HB-EGF and TGF-α, and promotes differentiation. In contrast, in samples incubated with the TACE inhibitor IC-3 or in cells isolated from TACE knock-out mice, mechanical strain did not release ligands or promote cell differentiation, which were both rescued after transfection of ADAM17. Cell adhesion assay and co-immunoprecipitation experiments in wild-type and TACE knock-out cells using several TACE constructs demonstrated not only that integrins α6 and β1 bind to TACE via the disintegrin domain but also that mechanical strain enhances these interactions. Furthermore, force applied to these integrin receptors by magnetic beads activated TACE and shed HB-EGF and TGF-α. The contribution of integrins α6 and β1 to differentiation of fetal epithelial cells by strain was demonstrated by blocking their binding site with specific antibodies and by culturing the cells on membranes coated with anti-integrin α6 and β1 antibodies. In conclusion, mechanical strain releases HB-EGF and TGF-α and promotes fetal type II cell differentiation via α6β1 integrin-ADAM17/TACE signaling pathway. These investigations provide novel mechanistic information on how mechanical forces promote fetal lung development and specifically differentiation of epithelial cells. This information could be also relevant to other tissues exposed to mechanical forces.

Basic Information on ADAM17

Ligand Name: ADAM metallopeptidase domain 17

Other Symbols: TACE, cSVP, CD156B

Ligand Location: cell membrane based on perplexity, uniprot

HGNC Gene Symbol Report: ADAM17

GeneCards: ADAM17

HGNC Gene Group: Metallopeptidases, CD molecules

Functional Annotations for ADAM17

Gene Ontologies: PAN-GO, AmiGO 2

Expression Profile: Human Protein Atlas (RNA and protein), Human Cell Atlas (RNA), GEPIA cancer vs normal (RNA), GeneCards (RNA and protein)

Disease Annotations: MalaCards, OMIM, Open Targets Platform, DISEASES (text mining), AI summary (LLM)

Interactions with other Receptors for ADAM17

ADAM17 — ITGA5 ・ ADAM17 — CD9 ・ ADAM17 — IL1R2 ・ ADAM17 — IL6R ・ ADAM17 — ITGA6 ・ ADAM17 — TNFRSF1A

Basic Information on ITGB1

Receptor Name: integrin subunit beta 1

Other Symbols: FNRB, MSK12, MDF2, CD29, GPIIA

Receptor Location: cell membrane based on hpa, perplexity, uniprot

HGNC Gene Symbol Report: ITGB1

GeneCards: ITGB1

HGNC Gene Group: CD molecules, Integrins

Functional Annotations for ITGB1

Gene Ontologies: PAN-GO, AmiGO 2

Expression Profile: Human Protein Atlas (RNA and protein), Human Cell Atlas (RNA), GEPIA cancer vs normal (RNA), GeneCards (RNA and protein)

Disease Annotations: MalaCards, OMIM, Open Targets Platform, DISEASES (text mining), AI summary (LLM)

Interactions with other Ligands for ITGB1

ADAM12 — ITGB1 ・ ADAM15 — ITGB1 ・ ADAM2 — ITGB1 ・ ADAM9 — ITGB1 ・ ANGPT1 — ITGB1 ・ CD14 — ITGB1 ・ CHAD — ITGB1 ・ COL11A1 — ITGB1 ・ COL18A1 — ITGB1 ・ COL1A1 — ITGB1 ・ COL1A2 — ITGB1 ・ COL2A1 — ITGB1 ・ COL3A1 — ITGB1 ・ COL4A1 — ITGB1 ・ COL4A3 — ITGB1 ・ COL4A4 — ITGB1 ・ COL4A5 — ITGB1 ・ COL4A6 — ITGB1 ・ COL5A1 — ITGB1 ・ CXCL12 — ITGB1 ・ F13A1 — ITGB1 ・ FBLN1 — ITGB1 ・ FBN1 — ITGB1 ・ FGA — ITGB1 ・ VEGFD — ITGB1 ・ FN1 — ITGB1 ・ HSPG2 — ITGB1 ・ ICAM4 — ITGB1 ・ LAMA1 — ITGB1 ・ LAMA2 — ITGB1 ・ LAMA4 — ITGB1 ・ LAMA5 — ITGB1 ・ LAMB1 — ITGB1 ・ LAMB3 — ITGB1 ・ LAMC1 — ITGB1 ・ LAMC2 — ITGB1 ・ LGALS3BP — ITGB1 ・ MATN1 — ITGB1 ・ MDK — ITGB1 ・ NID1 — ITGB1 ・ NPNT — ITGB1 ・ PLG — ITGB1 ・ RELN — ITGB1 ・ SEMA7A — ITGB1 ・ SPP1 — ITGB1 ・ TGM2 — ITGB1 ・ THBS1 — ITGB1 ・ THBS2 — ITGB1 ・ TIMP2 — ITGB1 ・ TNC — ITGB1 ・ VCAM1 — ITGB1 ・ VCAN — ITGB1 ・ VEGFA — ITGB1 ・ VEGFC — ITGB1 ・ VTN — ITGB1 ・ ANGPTL2 — ITGB1 ・ CCN4 — ITGB1 ・ CLEC11A — ITGB1 ・ LGALS1 — ITGB1 ・ PLA2G2A — ITGB1 ・ SPON2 — ITGB1 ・ ADAM28 — ITGB1 ・ AGGF1 — ITGB1 ・ AGRN — ITGB1 ・ ANGPT2 — ITGB1 ・ ANGPTL4 — ITGB1 ・ CCN2 — ITGB1 ・ CCN3 — ITGB1 ・ CD40LG — ITGB1 ・ CDH1 — ITGB1 ・ COL10A1 — ITGB1 ・ COL11A2 — ITGB1 ・ COL13A1 — ITGB1 ・ COL4A2 — ITGB1 ・ COL8A1 — ITGB1 ・ COL8A2 — ITGB1 ・ CSPG4 — ITGB1 ・ CX3CL1 — ITGB1 ・ ICAM5 — ITGB1 ・ IL1B — ITGB1 ・ JAM2 — ITGB1 ・ L1CAM — ITGB1 ・ LAMA3 — ITGB1 ・ LAMB2 — ITGB1 ・ LGALS3 — ITGB1 ・ LGALS8 — ITGB1 ・ MFGE8 — ITGB1 ・ MIA — ITGB1 ・ NTN4 — ITGB1 ・ PLAUR — ITGB1 ・ SVEP1 — ITGB1 ・ TGFB1 — ITGB1 ・ TGFB3 — ITGB1 ・ THBS4 — ITGB1 ・ THY1 — ITGB1 ・ TIMP1 — ITGB1 ・ VWF — ITGB1