CDB15:0001468 THBS1 — ITGB1

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

Title

Journal:; Year Published:

Abstract

Pro-adhesive and chemotactic activities of thrombospondin-1 for breast carcinoma cells are mediated by alpha3beta1 integrin and regulated by insulin-like growth factor-1 and CD98.

The Journal of biological chemistry, 1999; PubMed, Homo sapiens THBS1 — Homo sapiens ITGB1

ABSTRACT: Thrombospondin-1 (TSP1) is a matricellular protein that displays both pro- and anti-adhesive activities. Binding to sulfated glycoconjugates mediates most high affinity binding of soluble TSP1 to MDA-MB-435 cells, but attachment and spreading of these cells on immobilized TSP1 is primarily beta1 integrin-dependent. The integrin alpha3beta1 is the major mediator of breast carcinoma cell adhesion and chemotaxis to TSP1. This integrin is partially active in MDA-MB-435 cells but is mostly inactive in MDA-MB-231 and MCF-7 cells, which require beta1 integrin activation to induce spreading on TSP1. Integrin-mediated cell spreading on TSP1 is accompanied by extension of filopodia containing beta1 integrins. TSP1 binding activity of the alpha3beta1 integrin is not stimulated by CD47-binding peptides from TSP1 or by protein kinase C activation, which activate alphavbeta3 integrin function in the same cells. In MDA-MB-231 but not MDA-MB-435 cells, this integrin is activated by pertussis toxin, whereas serum, insulin, insulin-like growth factor-1, and ligation of CD98 increase activity of this integrin in both cell lines. Serum stimulation is accompanied by increased surface expression of CD98, whereas insulin-like growth factor-1 does not increase CD98 expression. Thus, the pro-adhesive activity of TSP1 for breast carcinoma cells is controlled by several signals that regulate activity of the alpha3beta1 integrin.

Recognition of the N-terminal modules of thrombospondin-1 and thrombospondin-2 by alpha6beta1 integrin.

The Journal of biological chemistry, 2003; PubMed, Homo sapiens THBS1 — Homo sapiens ITGB1

ABSTRACT: In addition to its recognition by alpha3beta1 and alpha4beta1 integrins, the N-terminal pentraxin module of thrombospondin-1 is a ligand for alpha6beta1 integrin. alpha6beta1 integrin mediates adhesion of human microvascular endothelial and HT-1080 fibrosarcoma cells to immobilized thrombospondin-1 and recombinant N-terminal regions of thrombospondin-1 and thrombospondin-2. alpha6beta1 also mediates chemotaxis of microvascular cells to thrombospondin-1 and thrombospondin-2. Using synthetic peptides, LALERKDHSG was identified as an alpha6beta1-binding sequence in thrombospondin-1. This peptide inhibited alpha6beta1-dependent cell adhesion to thrombospondin-1, thrombospondin-2, and the E8 fragment of murine laminin-1. The Glu residue in this peptide was required for activity, and the corresponding residue (Glu90) in the N-terminal module of thrombospondin-1 was required for its recognition by alpha6beta1, but not by alpha4beta1. alpha6beta1 was also expressed in human umbilical vein endothelial cells; but in these cells, only certain agonists could activate the integrin to recognize thrombospondins. Selective activation of alpha6beta1 integrin in microvascular endothelial cells by the anti-beta1 antibody TS2/16 therefore accounts for their adhesion responses to thrombospondins and explains the distinct functions of alpha4beta1 and alpha6beta1 integrins as thrombospondin receptors in microvascular and large vessel endothelial cells.

Alpha4beta1 integrin mediates selective endothelial cell responses to thrombospondins 1 and 2 in vitro and modulates angiogenesis in vivo.

Circulation research, 2004; PubMed, Homo sapiens THBS1 — Homo sapiens ITGB1

ABSTRACT: We examined the function of alpha4beta1 integrin in angiogenesis and in mediating endothelial cell responses to the angiogenesis modulators, thrombospondin-1 and thrombospondin-2. Alpha4beta1 supports adhesion of venous endothelial cells but not of microvascular endothelial cells on immobilized thrombospondin-1, vascular cell adhesion molecule-1, or recombinant N-terminal regions of thrombospondin-1 and thrombospondin-2. Chemotactic activities of this region of thrombospondin-1 and thrombospondin-2 are also mediated by alpha4beta1, whereas antagonism of fibroblast growth factor-2-stimulated chemotaxis is not mediated by this region. Immobilized N-terminal regions of thrombospondin-1 and thrombospondin-2 promote endothelial cell survival and proliferation in an alpha4beta1-dependent manner. Soluble alpha4beta1 antagonists inhibit angiogenesis in the chick chorioallantoic membrane and neovascularization of mouse muscle explants. The latter inhibition is thrombospondin-1-dependent and not observed in explants from thrombospondin-1-/- mice. Antagonizing alpha4beta1 may in part block proangiogenic activities of thrombospondin-1 and thrombospondin-2, because N-terminal regions of thrombospondin-1 and thrombospondin-2 containing the alpha4beta1 binding sequence stimulate angiogenesis in vivo. Therefore, alpha4beta1 is an important endothelial cell receptor for mediating motility and proliferative responses to thrombospondins and for modulation of angiogenesis.

Basic Information on THBS1

Ligand Name: thrombospondin 1

Other Symbols: TSP1, THBS, TSP, THBS-1, TSP-1

Ligand Location: secreted based on hpa, perplexity, uniprot, cell membrane based on hpa

HGNC Gene Symbol Report: THBS1

GeneCards: THBS1

HGNC Gene Group: Thrombospondin family

Functional Annotations for THBS1

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 THBS1

THBS1 — CD36 ・ THBS1 — CD47 ・ THBS1 — ITGA2B ・ THBS1 — ITGA3 ・ THBS1 — ITGA4 ・ THBS1 — ITGA6 ・ THBS1 — ITGB3 ・ THBS1 — LRP1 ・ THBS1 — SDC1 ・ THBS1 — SDC4 ・ THBS1 — PTPRJ ・ THBS1 — ITGA1 ・ THBS1 — ITGAV ・ THBS1 — SCARB2 ・ THBS1 — TGFBR1 ・ THBS1 — VLDLR

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 ・ ADAM17 — 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 ・ 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