CDB15:0001479 TIMP2 — ITGB1

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

Title

Journal:; Year Published:

Abstract

TIMP-2 mediated inhibition of angiogenesis: an MMP-independent mechanism.

Cell, 2003; PubMed, Homo sapiens TIMP2 — Homo sapiens ITGB1

ABSTRACT: Tissue inhibitors of metalloproteinases (TIMPs) suppress matrix metalloproteinase (MMP) activity critical for extracellular matrix turnover associated with both physiologic and pathologic tissue remodeling. We demonstrate here that TIMP-2 abrogates angiogenic factor-induced endothelial cell proliferation in vitro and angiogenesis in vivo independent of MMP inhibition. These effects require alpha 3 beta 1 integrin-mediated binding of TIMP-2 to endothelial cells. Further, TIMP-2 induces a decrease in total protein tyrosine phosphatase (PTP) activity associated with beta1 integrin subunits as well as dissociation of the phosphatase SHP-1 from beta1. TIMP-2 treatment also results in a concomitant increase in PTP activity associated with tyrosine kinase receptors FGFR-1 and KDR. Our findings establish an unexpected, MMP-independent mechanism for TIMP-2 inhibition of endothelial cell proliferation in vitro and reveal an important component of the antiangiogenic effect of TIMP2 in vivo.

Shp-1 mediates the antiproliferative activity of tissue inhibitor of metalloproteinase-2 in human microvascular endothelial cells.

The Journal of biological chemistry, 2006; PubMed, Homo sapiens TIMP2 — Homo sapiens ITGB1

ABSTRACT: The tissue inhibitors of metalloproteinases (TIMPs) regulate matrix metalloproteinase activity required for cell migration/invasion associated with cancer progression and angiogenesis. TIMPs also modulate cell proliferation in vitro and angiogenesis in vivo independent of their matrix metalloproteinase inhibitory activity. Here, we show that TIMP-2 mediates G1 growth arrest in human endothelial cells through de novo synthesis of the cyclin-dependent kinase inhibitor p27Kip1. TIMP-2-mediated inhibition of Cdk4 and Cdk2 activity is associated with increased binding of p27Kip1 to these complexes in vivo. Protein-tyrosine phosphatase inhibitors or expression of a dominant negative Shp-1 mutant ablates TIMP-2 induction of p27Kip1. Finally, angiogenic responses to fibroblast growth factor-2 and vascular endothelial growth factor-A in "motheaten viable" Shp-1-deficient mice are resistant to TIMP-2 inhibition, demonstrating that Shp-1 is an important negative regulator of angiogenesis in vivo.

Basic Information on TIMP2

Ligand Name: TIMP metallopeptidase inhibitor 2

Other Symbols: CSC-21K

Ligand Location: secreted based on perplexity, uniprot

HGNC Gene Symbol Report: TIMP2

GeneCards: TIMP2

HGNC Gene Group: Tissue inhibitor of metallopeptidases

Functional Annotations for TIMP2

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 TIMP2

TIMP2 — ITGA3 ・ TIMP2 — MMP14 ・ TIMP2 — MMP2

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 ・ THBS1 — ITGB1 ・ THBS2 — 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