Disease relevance of Itgb1

• By eliminating the beta 1 integrin gene through homologous recombination, we have assessed the role of the beta 1 integrin family in the F9 embryonal carcinoma model for endodermal differentiation [1].
• These data suggest that beta 1 integrin links laminin in the basal lamina to the cytoskeleton in order for Schwann cells to ensheath axons, and alteration of this linkage contributes to the peripheral neuropathy of congenital muscular dystrophy [2].
• The metastasis potential of all three beta1 integrin-expressing GERM 11 sublines tested was significantly higher than that of the beta1-deficient GERM 11 cells [3].
• Chemokine receptor CXCR4-beta1 integrin axis mediates tumorigenesis of osteosarcoma HOS cells [4].
• The expression of a transgene coding for a chimeric molecule, containing the cytoplasmic and transmembrane domains of the beta1-integrin chain and the extracellular domain of the T-cell differentiation antigen CD4, was targeted to the mouse mammary gland by the mouse mammary tumor virus (MMTV) promoter [5].

High impact information on Itgb1

• The expression of beta1 integrin, which is preferentially expressed in epidermal stem cells is unusually low in the epidermis of K14.MYC2 mice [6].
• We conclude that deregulated expression of c-Myc in stem cells reduces beta1 integrin expression, which is essential to both keratinocyte migration and stem cell maintenance [6].
• Unliganded integrins are not associated with the rearward-moving cytoskeleton: gold particles attached to beta1 integrin by a monoclonal antibody diffuse in the membrane [7].
• Here we report that chimaeric mice generated with beta1-integrin-deficient embryonic stem (ES) cells lack beta1(-/-) cells in blood and in haematopoietic organs such as spleen, thymus and bone marrow [8].
• To assess the functions of beta1 integrin during skeletogenesis, we inactivated the beta1 integrin gene in chondrocytes [9].

Chemical compound and disease context of Itgb1

• A beta1 integrin-specific antibody, but not antibodies specific for other integrin subunits, inhibited reovirus infection of HeLa cells [10].
• By 6 months of age, mice with depressed ventricular expression of beta1 integrin developed a dilated cardiomyopathy that was not evident in any control animals and had patchy decrease in glucose metabolism as determined by positron emission tomography [11].
• In addition, we also studied the influence of melatonin on the expression of two cell surface adhesion molecules (E-cadherin and beta1 integrin) and an intermediate filament protein (vimentin), the expression of which has been correlated with the relative invasive capacity of human breast cancer cells [12].
• Engrafted glioma cells expressed laminin, LBP110 and beta 1 integrin antigens, indicating the molecular mechanisms of C6 motility observed in culture may contribute to glioma invasion in vivo [13].
• The deletion of beta1 integrin resulted in resistance to bleomycin-induced fibrosis [14].

Biological context of Itgb1

• Altogether these findings establish that beta1-integrin-dependent motility and proliferation of chondrocytes are mandatory events for endochondral bone formation to occur [9].
• Combined inhibition of beta1 integrin and either PI3K or MAPK resulted in nearly complete phenotypic reversion (MDA-MB-231, MCF7) or in cell death (Hs578T) [15].
• These data suggest that the NPXY motifs of the beta1 integrin tail are essential for beta1 integrin function, whereas tyrosine phosphorylation and the membrane-proximal salt bridge between alpha and beta1 tails have no apparent function under physiological conditions in vivo [16].
• Tyrosine-to-alanine substitutions abolished beta1 integrin functions and led to a beta1 integrin-null phenotype in vivo [16].
• Luminal cell proliferation was strongly inhibited in beta1 integrin mutant glands, which correlated with a specific increase of p21 Cip1 expression [17].

Anatomical context of Itgb1

• In the absence of Itgb1 expression in skeletal muscle, interactions between motor neurons and muscle are defective, preventing normal presynaptic differentiation [18].
• We conclude that Itgb1 expression in muscle, but not in motor neurons, is critical for NMJ development [18].
• These results point to the essential role of beta1 integrin signaling in mammary epithelial cell proliferation [17].
• In the beta1 integrin mutant mammary gland, individual alveoli were disorganized resulting from alterations in cell-basement membrane associations [17].
• Conditional disruption of beta 1 integrin in Schwann cells impedes interactions with axons [2].

Associations of Itgb1 with chemical compounds

• Blocking of beta1 integrin or VCAM-1, the ligand of alpha4beta1 integrin, inhibits PP formation [19].
• High glucose and angiotensin II increase beta1 integrin and integrin-linked kinase synthesis in cultured mouse podocytes [20].
• The adhesion activity of HEK293T cells to CNR1 EC-Fc fusion protein was completely blocked by inhibitors of integrins, including RGDS peptide and anti-beta1 integrin antibodies [21].
• To distinguish primary from secondary consequences of beta1 integrin loss, we compared epidermal beta1 deletion at E14.5 via K5Cre and 4-hydroxy-tamoxifen induced deletion in adulthood via K14CreER [22].
• Myocyte membrane integrity as determined via Evan's blue dye staining was disrupted in the beta1 integrin knockout mice [11].
• A significant reduction in the total number of BM-MSC in the infarcted myocardium was observed after integrin beta1 blockade but not integrin alpha4 or CXCR4 blockade [23].

Physical interactions of Itgb1

• Phosphatidylinositol phosphate kinase type 1gamma and beta1-integrin cytoplasmic domain bind to the same region in the talin FERM domain [24].
• We show that Shh directly binds to laminin and that laminin-Shh induced cell proliferation is dependent on beta1 integrin expression in GCPs [25].
• PTP1B coimmunoprecipitates with beta1-integrin from nonionic detergent extracts and colocalizes with vinculin and the ends of actin stress fibers in focal adhesions [26].
• Using a biochemical method to quantify bound integrins in cultured cells, we found that differences in Fn conformation altered the quantity of bound alpha5 and beta1 integrin subunits but not alphav or beta3 [27].
• Attachment of human pre-B leukaemic cells to human or murine bone marrow stromal cells in vitro is largely mediated by the beta1 integrin VLA-4 binding to VCAM-1 [28].

Enzymatic interactions of Itgb1

• We also assessed the role of serine phosphorylation in the regulation of alpha 6A beta 1 integrin function by site-directed mutagenesis of the two serine residues present in the alpha 6A cytoplasmic domain because this domain is phosphorylated on serine residues in response to stimuli that activate the laminin receptor function of alpha 6 A beta 1 [29].

Regulatory relationships of Itgb1

• In addition, the up-regulation of ILK synthesis induced by these stimuli was related to beta1 integrin synthesis and increased ILK kinase activity [20].
• Induction of MMP-13 expression by collagen was potently and synergistically inhibited by blocking antibodies against alpha1 and beta1 integrin subunits, indicating that alpha1beta1 integrin mediates the MMP-13-inducing cellular signal generated by three-dimensional type I collagen [30].
• Low density lipoprotein receptor-related protein-1 promotes beta1 integrin maturation and transport to the cell surface [31].
• This suggests that the local association of talin with these sites is induced by the cytoplasmic tail of beta 1 integrin receptor presented by the chimeric protein [32].
• Specific beta1 integrin site selectively regulates Akt/protein kinase B signaling via local activation of protein phosphatase 2A [33].

Other interactions of Itgb1

• A connection between p21 Cip1 and beta1 integrin as well as FAK was also established in primary mammary cells [17].
• Defective Rac-mediated proliferation and survival after targeted mutation of the beta1 integrin cytodomain [34].
• Epidermal growth factor activation of vinculin and beta 1-integrin gene transcription in quiescent Swiss 3T3 cells. Regulation through a protein kinase C-independent pathway [35].
• Notch, epidermal growth factor receptor, and beta1-integrin pathways are coordinated in neural stem cells [36].
• Furthermore, direct activation of protein kinase C with 1,2-myristate 1,3-acetate did not induce the expression of vinculin or beta 1-integrin mRNA, but did activate c-fos expression [35].

Analytical, diagnostic and therapeutic context of Itgb1

• Here we report that mutation by gene targeting of the cytoplasmic tail of beta1 integrin leads to defective proliferation and survival both in vivo and in vitro [34].
• Immunoprecipitation of extracts from embryonic kidney with antibodies against alpha 6 subunit yielded bands corresponding to the expected size of beta 1 integrin subunit but not of beta 4 subunit [37].
• Tumors were induced by subcutaneous injection of GERM 11 cells and 3 independent beta1 integrin expressing sublines (GERM 116, 1A10, 2F2) into syngeneic mice [3].
• The intracellular signals initiated by beta 3 integrins in lymphocytes are not well characterized, but in many cell types, beta 1 integrin ligation activates mitogen-activated protein (MAP) kinases [38].
• To investigate beta1-integrin activity, integrin-linked kinase (ILK) expression was measured by immunoblotting [39].

References