SEARCH · PubMed Health

Results for “Integrin”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,099 records · Page 61Linked to original sources

PubMed1998

Role of integrins in the attachment of metastatic follicular thyroid carcinoma cell lines to bone.

One of the principle targets for metastasis of follicular thyroid carcinoma (FTC) is the skeleton. Because no data are available on the role of the integrin adhesion molecule family in the attachment of FTC to bone, we studied the attachment characteristics of three FTC cell lines to bone and the role of integrins. Three cell lines were used from the same patient, one (FTC-133) from the primary tumor and two (FTC-236 and FTC-238) from metastases. Attachment of FTC cell lines to bone was assessed on conditioned medium of an osteoblastic cell line, coated onto plastic, as an in vitro model of bone matrix. The synthetic RGD (Arg-Gly-Asp) peptide GRGDS impaired attachment of the FTC cell lines to bone matrix, demonstrating the role of integrins in the attachment of FTC to bone. Attachment of FTC-133 to bone matrix was blocked completely by GRGDS, whereas attachment of FTC-236 and FTC-238 could not be impaired completely. Semiquantitative polymerase chain reaction (PCR) of cDNA from the cell lines indicated stronger expression of alpha5 integrin mRNA in FTC-133 than in the other cell lines. In line with this, attachment of FTC-133 to bone matrix could be inhibited almost completely by anti alpha5 and beta1 integrin antibodies, indicating the importance of the fibronectin receptor in the attachment of FTC-133 to bone. Binding of FTC-236 and FTC-238 to bone matrix could not be inhibited completely by anti-integrin antibodies, suggesting an additional role of nonintegrin adhesion molecules in the attachment of FTC-236 and FTC-238 to bone. The synthetic bone sialoprotein cyclic peptide, CNB, revealed antiadhesive effects in the binding of FTC to bone. In conclusion, integrins play an important role in the attachment of metastatic FTC to bone. Differences in the functional involvement of integrins in the attachment to bone are observed between the three cell lines studied. From the present results, antiadhesive interventions with synthetic RGD peptides in FTC may be designed.

Adenocarcinoma, Follicular↗

PubMed2003

Clustering induces a lateral redistribution of alpha 2 beta 1 integrin from membrane rafts to caveolae and subsequent protein kinase C-dependent internalization.

Integrin alpha 2 beta 1 mediates the binding of several epithelial and mesenchymal cell types to collagen. The composition of the surrounding plasma membrane, especially caveolin-1- and cholesterol-containing membrane structures called caveolae, may be important to integrin signaling. On cell surface alpha 2 beta 1 integrin was located in the raft like membrane domain, rich in GPI-anchored proteins, rather than in caveolae. However, when antibodies were used to generate clusters of alpha 2 beta 1 integrin, they started to move laterally on cell surface along actin filaments. During the lateral movement small clusters fused together. Finally alpha 2 beta 1 integrin was found inside caveolae and subsequently internalized into caveosome-like perinuclear structures. The internalization process, unlike cluster formation or lateral redistribution, was dependent on protein kinase C alpha activity. Caveolae are known to be highly immobile structures and alpha 2 beta 1 integrin clusters represent a previously unknown mechanism to activate endocytic trafficking via caveolae. The process was specific to alpha 2 beta 1 integrin, because the antibody-mediated formation of alpha V integrin clusters activated their internalization in coated vesicles and early endosomes. In addition to natural ligands human echovirus-1 (EV1) gains entry into the cell by binding to alpha 2 beta 1 and taking advantage of alpha 2 beta 1 internalization via caveolae.

Actin Cytoskeleton↗

PubMed2004

Cross-talk of integrin alpha3beta1 and tissue factor in cell migration.

In cancer and angiogenesis, coagulation-independent roles of tissue factor (TF) in cell migration are incompletely understood. Immobilized anti-TF extracellular domain antibodies induce cell spreading, but this phenomenon is epitope specific and is not induced by anti-TF 5G9. Spreading on anti-TF is beta1 integrin-dependent, indicating functional interactions of the TF extracellular domain 5G9 epitope (a presumed integrin-binding site) and integrins. Recombinant TF extracellular domain supports adhesion of cells expressing alphavbeta3 or certain beta1 integrin heterodimers (alpha3beta1, alpha4beta1, alpha5beta1, alpha6beta1, alpha9beta1) and adhesion is blocked by specific anti-integrin antibodies or mutations in the integrin ligand-binding site. Although several studies have linked TF to cell migration, we here demonstrate that TF specifically regulates alpha3beta1-dependent migration on laminin 5. Expression of TF suppresses alpha3beta1-dependent migration, but only when the TF cytoplasmic domain is not phosphorylated. Suppression of migration can be reversed by 5G9, presumably by disrupting integrin interaction, or by the protease ligand VIIa, known to induce PAR-2-dependent phosphorylation of TF. In both cases, release of alpha3beta1 inhibition is prevented by mutation of critical phosphorylation sites in the TF cytoplasmic domain. Thus, TF influences integrin-mediated migration through cooperative intra- and extracellular interactions and phosphorylation regulates TF's function in cell motility.

Animals↗

PubMed1998

Genetic analysis of the Drosophila alphaPS2 integrin subunit reveals discrete adhesive, morphogenetic and sarcomeric functions.

The integrin family of cell surface receptors mediates cell-substrate and cell-to-cell adhesion and transmits intracellular signals. In Drosophila there is good evidence for an adhesive role of integrins, but evidence for integrin signalling has remained elusive. Each integrin is an alphabeta heterodimer, and the Drosophila betaPS subunit forms at least two integrins by association with different alpha subunits: alphaPS1betaPS (PS1) and alphaPS2betaPS (PS2). The complex pattern of PS2 integrin expression includes, but is more extensive than, the sites where PS2 has a known requirement. In order to investigate whether PS2 integrin is required at these additional sites and/or has functions besides mediating adhesion, a comprehensive genetic analysis of inflated, the gene that encodes alphaPS2, was performed. We isolated 35 new inflated alleles, and obtained 10 alleles from our colleagues. The majority of alleles are amorphs (36/45) or hypomorphs (4/45), but five alleles that affect specific developmental processes were identified. Interallelic complementation between these alleles suggests that some may affect distinct functional domains of the alphaPS2 protein, which specify particular interactions that promote adhesion or signalling. One new allele reveals that the PS2 integrin is required for the development of the adult halteres and legs as well as the wing.

Alleles↗

PubMed2003

Alteration of integrin expression by glial cell line-derived neurotrophic factor (GDNF) in human pancreatic cancer cells.

INTRODUCTION: Pancreatic cancer cells express a number of functionally active integrins that are related to their adhesive and invasive abilities. AIMS: To determine whether glial cell line-derived neurotrophic factor (GDNF) influences the expression of integrins in pancreatic cancer cell lines and to elucidate the mechanisms of adhesion and invasion to extracellular matrix (ECM) proteins. METHODOLOGY: The expression of integrin subunits and the alteration of their expression by GDNF were examined by flow-cytometric analysis and cellular enzyme-linked immunosorbent assay in pancreatic cancer cell lines (MIA PaCa-2 and BxPC-3). Assays of adhesion and invasion of cancer cells to ECM proteins were conducted to investigate whether increased integrin expression affects the interaction between cancer cells and putative integrin ECM ligands. RESULTS: Expression of some of the integrin subunits in pancreatic cancer cells was enhanced by GDNF. The enhancement and associated increase in adhesive and invasive ability by GDNF were inhibited by blocking the GDNF receptor or the integrin beta1 subunit. CONCLUSIONS: In pancreatic cancer, the enhancement of integrin expression by GDNF signaling through the GDNF receptor strongly influences adhesion and invasion to ECM proteins.

Antibodies↗

PubMed2002

Monoclonal antibody against beta7 integrins, but not beta7 deficiency, attenuates intestinal allograft rejection in mice.

BACKGROUND: beta7 integrins mediate homing and retention of lymphocytes to the normal and inflamed small bowel in a tissue-selective fashion. In the present study, we investigated the expression of beta7 integrins after small bowel transplantation (SBT) and tested the effects of blocking beta7-mediated pathways by using monoclonal antibody (mAb) or knockout mice. METHODS: Heterotopic SBT from BALB/c to C57BL/6 (B6) was used as a surgical model. Expression of beta7 integrins was measured on recipient lymphocytes (CD4 and CD8 ) in spleen, blood, and mesenteric lymph nodes (MLN) using flow cytometry. To analyze the effects of blocking beta7 integrins on graft survival, either beta7-deficient B6 or wild-type B6 mice that were treated with mAb against beta7 were studied. RESULTS: After allogeneic SBT, there were markedly increased levels of alpha4beta7 recipient CD8 lymphocytes in MLN, blood, and spleen as early as 3 days postoperatively. In contrast, alpha4beta7 integrin levels in isograft recipients were similar to those of normal mice. Mean survival time of intestinal allografts was not affected by beta7 deficiency (7.3+/-1 days) compared with wild-type mice (7.5+/-0.8 days). However, mAb against beta7 integrins significantly prolonged graft survival (12.8+/-1 days) compared with treatment with control mAb (7.3+/-1 days, <0.001). Histologic changes of SBT rejection were significantly attenuated when mice were given mAb against beta7. CONCLUSION: As indicated by the increased levels of alpha4beta7 CD8 lymphocytes, activation of this integrin contributes to the immune response in SBT rejection. Furthermore, blocking beta7 integrins with mAb provides a suitable target for immunosuppressive therapy. The discrepancy in survival data obtained by mAb and beta7 deficiency may be a result of the more rapid activation of compensatory mechanisms in the knockout mice.

Animals↗

PubMed2006

Integrin alpha3 subunit participates in myoblast adhesion and fusion in vitro.

Satellite cells are myogenic precursor cells, participating in growth, and regeneration of skeletal muscles. The proteins that play a role in myogenesis are integrins. In this report, we show that the integrin alpha3 subunit is expressed in quiescent satellite cells and activated myoblasts. We also find that in myoblasts the integrin alpha3 subunit is localized at cell-cell and cell-extracellular matrix contacts. We notice that increase in protein and mRNA encoding the integrin alpha3 subunit accompanies myoblast differentiation. Using double immunofluorescence and immunoprecipitation experiments, we demonstrate that the integrin alpha3 subunit co-localizes with actin, and binds the integrin beta1 subunit and ADAM12, suggesting that the complex alpha3beta1/ADAM12 is probably involved in myoblast fusion. Importantly, overexpression of the full-length integrin alpha3 subunit increases myoblast fusion whereas an antibody against its extracellular domain inhibits fusion. These data demonstrate that the integrin alpha3 subunit may contribute to satellite cell activation and then myoblast adhesion and fusion.

ADAM Proteins↗

PubMed1999

Alteration of integrin expression in oral squamous cell carcinomas.

OBJECTIVE: This study examines the intensity of expression of beta 1, alpha 2, alpha 3, alpha 5, alpha 6 integrin subunits in oral squamous cell carcinoma (SCC) as opposed to normal oral epithelium, and the intensity of expression and distribution pattern of the above subunits in relation to tumour differentiation grade. MATERIALS AND METHODS: Cryostat sections of 25 cases of oral SCC and 15 cases of normal oral epithelium were studied by immunohistochemistry (APAAP method). RESULTS: The intensity of expression of beta 1, alpha 2 (Pearson chi 2 P < 0.001) and alpha 6 (Test for Trend P < 0.05) integrin subunits was reduced significantly in SCC compared to normal oral epithelium. All integrin subunits were mainly expressed in the peripheral cell layer of tumour islands. No correlation was found between the intensity of integrin expression and the degree of differentiation in SCC. The same applied to the distribution pattern of the integrin subunits. By means of cross examination of all integrins, the loss of intensity of alpha 2 beta 1 integrin expression was found to have the strongest correlation with oral SCC (Ordered Logistic Regression). CONCLUSIONS: Reduced intensity of expression of all subunits was found in oral SCC compared to normal epithelium. Further investigation is needed to determine whether alpha 2 beta 1 integrin expression can be used as a prognostic evaluator for the behaviour of the disease.

Carcinoma, Squamous Cell↗

PubMed2004

Interactions of foot-and-mouth disease virus with soluble bovine alphaVbeta3 and alphaVbeta6 integrins.

At least four members of the integrin family of receptors, alphaVbeta1, alphaVbeta3, alphaVbeta6, and alphaVbeta8, have been identified as receptors for foot-and-mouth disease virus (FMDV) in vitro. Our investigators have recently shown that the efficiency of receptor usage appears to be related to the viral serotype and may be influenced by structural differences on the viral surface (H. Duque and B. Baxt, J. Virol. 77:2500-2511, 2003). To further examine these differences, we generated soluble alphaVbeta3 and alphaVbeta6 integrins. cDNA plasmids encoding the individual complete integrin alphaV, beta3, and beta6 subunits were used to amplify sequences encoding the subunits' signal peptide and ectodomain, resulting in subunits lacking transmembrane and cytoplasmic domains. COS-1 cells were transfected with plasmids encoding the soluble alphaV subunit and either the soluble beta3 or beta6 subunit and labeled with [35S]methionine-cysteine. Complete subunit heterodimeric integrins were secreted into the medium, as determined by radioimmunoprecipitation with specific monoclonal and polyclonal antibodies. For the examination of the integrins' biological activities, stable cell lines producing the soluble integrins were generated in HEK 293A cells. In the presence of divalent cations, soluble alphaVbeta6 bound to representatives of type A or O viruses, immobilized on plastic dishes, and significantly inhibited viral replication, as determined by plaque reduction assays. In contrast, soluble alphaVbeta3 was unable to bind to immobilized virus of either serotype; however, virus bound to the immobilized integrin, suggesting that FMDV binding to alphaVbeta3 is a low-affinity interaction. In addition, soluble alphaVbeta3 did not neutralize virus infectivity. Incubation of soluble alphaVbeta6 with labeled type A12 or O1 resulted in a significant inhibition of virus adsorption to BHK cells, while soluble alphaVbeta3 caused a low (20 to 30%), but consistent, inhibition of virus adsorption. Virus incubated with soluble alphaVbeta6 had a lower sedimentation rate than native virus on sucrose density gradients, but the particles retained all of their structural proteins and still contained bound integrin and, therefore, were not exhibiting characteristics of a picornavirus A particle.

Animals↗

PubMed2003

R-Ras promotes focal adhesion formation through focal adhesion kinase and p130(Cas) by a novel mechanism that differs from integrins.

R-Ras regulates integrin function, but its effects on integrin signaling pathways have not been well described. We demonstrate that activation of R-Ras promoted focal adhesion formation and altered localization of the alpha2beta1 integrin from cell-cell to cell-matrix adhesions in breast epithelial cells. Constitutively activated R-Ras(38V) dramatically enhanced focal adhesion kinase (FAK) and p130(Cas) phosphorylation upon collagen stimulation or clustering of the alpha2beta1 integrin, even in the absence of increased ligand binding. Signaling events downstream of R-Ras differed from integrins and K-Ras, since pharmacological inhibition of Src or disruption of actin inhibited integrin-mediated FAK and p130(Cas) phosphorylation, focal adhesion formation, and migration in control and K-Ras(12V)-expressing cells but had minimal effect in cells expressing R-Ras(38V). Therefore, signaling from R-Ras to FAK and p130(Cas) has a component that is Src independent and not through classic integrin signaling pathways and a component that is Src dependent. R-Ras effector domain mutants and pharmacological inhibition suggest a partial role for phosphatidylinositol 3-kinase (PI3K), but not Raf, in R-Ras signaling to FAK and p130(Cas). However, PI3K cannot account for the Src-independent pathway, since simultaneous inhibition of both PI3K and Src did not completely block effects of R-Ras on FAK phosphorylation. Our results suggest that R-Ras promotes focal adhesion formation by signaling to FAK and p130(Cas) through a novel mechanism that differs from but synergizes with the alpha2beta1 integrin.

Actins↗

PubMed2004

Protein kinase B/Akt acts via glycogen synthase kinase 3 to regulate recycling of alpha v beta 3 and alpha 5 beta 1 integrins.

Protein kinase B (PKB)/Akt is known to promote cell migration, and this may contribute to the enhanced invasiveness of malignant cells. To elucidate potential mechanisms by which PKB/Akt promotes the migration phenotype, we have investigated its role in the endosomal transport and recycling of integrins. Whereas the internalization of alpha v beta 3 and alpha 5 beta 1 integrins and their transport to the recycling compartment were independent of PKB/Akt, the return of these integrins (but not internalized transferrin) to the plasma membrane was regulated by phosphatidylinositol 3-kinases and PKB/Akt. The blockade of integrin recycling and cell spreading on integrin ligands effected by inhibition of PKB/Akt was reversed by inhibition of glycogen synthase kinase 3 (GSK-3). Moreover, expression of nonphosphorylatable active GSK-3 beta mutant GSK-3 beta-A9 suppressed recycling of alpha 5 beta 1 and alpha v beta 3 and reduced cell spreading on ligands for these integrins, indicating that PKB/Akt promotes integrin recycling by phosphorylating and inactivating GSK-3. We propose that the ability of PKB/Akt to act via GSK-3 to promote the recycling of matrix receptors represents a key mechanism whereby integrin function and cell migration can be regulated by growth factors.

Animals↗

PubMed2005

Biological and molecular properties of a new alpha(v)beta3/alpha(v)beta5 integrin antagonist.

The aim of the present study was to identify specific alpha(v)beta3/alpha(v)beta5 integrin antagonists active on tumor-induced angiogenesis. To this purpose, in vitro integrin-binding assays were used to screen a library of conformationally constrained bicyclic lactam Arg-Gly-Asp-containing pseudopeptides. The results identified ST1646 as a high-affinity specific ligand for alpha(v)beta3 and alpha(v)beta5 integrins with negligible interacting with alpha5beta1 integrin. In all the assays, ST1646 was equipotent to or more potent than the well-characterized integrin antagonists c(RGDfV) and cyclo(Arg-Gly-Asp-d-Phe-[NMe]Val) (EMD121974). In the chorioallantoic membrane assay, topical administration of ST1646 was able to prevent the angiogenic responses elicited by recombinant fibroblast growth factor-2 or vascular endothelial growth factor. In addition, systemic administration of ST1646 in mice exerted a significant antiangiogenic activity on neovascularization triggered by mammary carcinoma MDA-MB435 cells implanted s.c. in a dorsal air sac via a (Millipore Filter Corporation, Bedford, MA) chamber. Moreover, ST1646 delivery via an osmotic pump inhibited the growth and vascularization of tumor xenografts originating from the injection of alpha(v)beta3/alpha(v)beta5-expressing human ovarian carcinoma cells in nude mice. In agreement with the biochemical and pharmacologic studies, Monte Carlo/Stochastic Dynamics simulation showed that the bicyclic scaffold in ST1646 forced the compound to assume a preferred conformation superimposable to the X-ray conformation of alpha(v)beta3-bound EMD121974. Accordingly, computer-docking studies indicated that the ST1646-alpha(v)beta3 integrin complex maintains the ligand-receptor distances and interactions observed in the crystalline EMD121974-alpha(v)beta3 integrin complex. Taken together, these observations indicate that ST1646 represents a dual alpha(v)beta3/alpha(v)beta5 integrin antagonist with interesting biochemical and biological features to be tested in cancer therapy.

Animals↗

PubMed2006

Platelet-derived growth factor BB-mediated normalization of dermal interstitial fluid pressure after mast cell degranulation depends on beta3 but not beta1 integrins.

Interstitial fluid pressure (PIF) is one of the determinants of transcapillary fluid flux and thereby interstitial fluid volume. Cell-mediated control of PIF regulates fluid content in the loose interstitial connective tissues that surround the capillary bed. To maintain a normal PIF in dermis, beta1 integrins mediate the tensile strength applied by connective tissue cells on the extracellular matrix. Platelet-derived growth factor (PDGF)-BB normalizes anaphylaxis-induced reduction of PIF. Anti-beta3 integrin IgG and a cyclic RGD peptide that inhibits the alphaVbeta3 integrin blocked the ability of PDGF-BB to normalize the lowered PIF resulting from mast cell degranulation. PDGF-BB was unable to normalize PIF lowered as a result of mast cell degranulation in beta3-negative mice. Monoclonal anti-beta3 integrin IgG had no effect on PIF in normal mouse dermis. In contrast, administration of anti-beta1 integrin IgM lowered PIF in normal dermis but had no effect on PDGF-BB-induced normalization of PIF after anaphylaxis. Furthermore, collagen gel contraction mediated by wild-type mouse embryonal fibroblasts were only marginally affected by function-blocking anti-beta1 integrin antibodies, especially in the presence of PDGF-BB. In contrast, contraction mediated by alphaV-negative mouse embryonic fibroblasts was completely blocked by anti-beta1 integrin antibodies, even after stimulation with PDGF-BB. These results show a previously unrecognized in vivo function for the alphaVbeta3 integrin, as a participant in the control of PIF during inflammatory reactions. Furthermore, our data demonstrate that PDGF-BB induces connective tissue cells to generate tensile forces via alphaVbeta3 during such reactions.

Animals↗

PubMed2005

Transglutaminase-mediated oligomerization of the fibrin(ogen) alphaC domains promotes integrin-dependent cell adhesion and signaling.

Interactions of endothelial cells with fibrin(ogen) are implicated in inflammation, angiogenesis, and wound healing. Cross-linking of the fibrinogen alphaC domains with factor XIIIa generates ordered alphaC oligomers mimicking polymeric arrangement of the alphaC domains in fibrin. These oligomers and those prepared with tissue transglutaminase were used to establish a mechanism of the alphaC domain-mediated interaction of fibrin with endothelial cells. Cell adhesion and chemical cross-linking experiments revealed that oligomerization of the alphaC domains by both transglutaminases significantly increases their RGD (arginyl-glycyl-aspartate)-dependent interaction with endothelial alphaVbeta3 and to a lesser extent with alphaVbeta5 and alpha5beta1 integrins. The oligomerization promotes integrin clustering, thereby increasing cell adhesion, spreading, formation of prominent peripheral focal contacts, and integrin-mediated activation of focal adhesion kinase (FAK) and extracellular signal-regulated kinase (ERK) signaling pathways. The enhanced integrin clustering is likely caused by ordered juxtaposition of RGD-containing integrin-binding sites upon oligomerization of the alphaC domains and increased affinity of these domains for integrins. Our findings provide new insights into the mechanism of the alphaC domain-mediated interaction of endothelial cells with fibrin and imply its potential involvement in cell migration. They also suggest a new role for transglutaminases in regulation of integrin-mediated adhesion and signaling via covalent modification of integrin ligands.

Animals↗

PubMed1997

Laminin suppresses progesterone production by human luteinizing granulosa cells via interaction with integrin alpha 6 beta 1.

We previously raised a murine monoclonal antibody (mAb), OG-1, against human granulosa cells (GC) and reported that human GC express the OG-1 antigen with the highest immunoreactivity during the periovulatory phase. Later, we showed that the OG-1 antigen is identical to human integrin alpha 6, and that human GC express integrin alpha 6 beta 1, but not alpha 6 beta 4. In the present study, we examined the expression of laminin (LN), the ligand for integrin alpha 6 beta 1. Flow cytometry showed that LN was bound to the cell surface of some GC obtained from preovulatory follicles of patients undergoing in vitro fertilization. Immunohistochemistry showed that LN was detected between luteinizing GC in the early corpora lutea. To examine the effect of LN on steroidogenesis by human luteinizing GC, GC obtained from patients undergoing in vitro fertilization were cultured on mouse LN-coated or noncoated plastic dishes in medium containing 5% FCS for 24 h. In the absence or presence in hCG (1 IU/mL), GC cultured on LN-coated dishes produced 0.70- and 0.67-fold less progesterone than those on noncoated dishes, respectively (P < 0.05). We examined the effect of the interaction of integrin alpha 6 beta 1 and LN on steroidogenesis by human luteinizing GC. We cultured GC with 5 micrograms/mL of the anti-alpha 6 mAb GoH3, which inhibits the interaction between human integrin alpha 6 beta 1 and mouse LN, or with a control rat mAb (TER199) on mouse LN-coated dishes in serum-free medium for 24 h. In the absence or presence of hCG (1 IU/mL), GC cultured with GoH3 produced 1.97- and 1.94-fold more progesterone than the control cells (P < 0.01 and P < 0.05, respectively). In contrast, when GC were cultured on dishes coated with type IV collagen, progesterone production was not enhanced by GoH3. Furthermore, the anti-alpha 6 mAb OG-1, which does not inhibit the interaction between integrin alpha 6 beta 1 and LN, had no effect on the progesterone production by GC cultured on LN. These results indicate that LN suppresses the luteinization of human luteinizing GC via integrin alpha 6 beta 1 and that integrin alpha 6 beta 1 regulates the luteinization of human GC during the periovulatory phase.

Adult↗

PubMed1994

A developmental analysis of oligodendroglial integrins in primary cells: changes in alpha v-associated beta subunits during differentiation.

We have examined the expression of integrins on primary oligodendroglial cells during the differentiation of the proliferative oligodendrocyte precursor (O-2A progenitor) cell to the postmitotic oligodendrocyte. Cells of the oligodendrocyte lineage expressed a limited repertoire of integrins: alpha 6 beta 1 and alpha v integrins including alpha v beta 1, alpha v beta 3 and alpha v beta 5, as well as a potentially novel integrin alpha v beta 80 kDa. Integrin expression was developmentally regulated; during differentiation alpha v beta 1 was reduced and alpha v beta 5 upregulated. These results suggest that laminin and vitronectin are important extracellular matrix ligands for oligodendrocytes, and provide a rational explanation for previous observations that RGD peptides inhibit the expression of myelin-specific genes. They also suggest a simple model by which switching of integrin beta subunits might regulate differentiation. As chimeric beta 1 integrins with a beta 5 cytoplasmic domain support proliferation less well than normal beta 1 integrins (Pasqualini and Hemler (1994), J. Cell Biol. 125, 447-460) the switch from alpha v beta 1 to alpha v beta 5 might play a key instructive role in the cessation of proliferation and subsequent differentiation.

Animals↗

PubMed1999

Migration of the Drosophila primordial midgut cells requires coordination of diverse PS integrin functions.

Cell migration during embryogenesis involves two populations of cells: the migrating cells and the underlying cells that provide the substratum for migration. The formation of the Drosophila larval midgut involves the migration of the primordial midgut cells along a visceral mesoderm substratum. We show that integrin adhesion receptors are required in both populations of cells for normal rates of migration. In the absence of the PS integrins, the visceral mesoderm is disorganised, the primordial midgut cells do not display their normal motile appearance and their migration is delayed by 2 hours. Removing PS integrin function from the visceral mesoderm alone results in visceral mesoderm disorganization, but only causes a modest delay in migration and does not affect the appearance of the migrating cells. Removing PS integrin function from the migrating cells causes as severe a delay in migration as the complete loss of PS integrin function. The functions of PS1 and PS2 are specific in the two tissues, endoderm and mesoderm, since they cannot substitute for each other. In addition there is a partial redundancy in the function of the two PS integrins expressed in the endoderm, PS1 (alphaPS1betaPS) and PS3 (alphaPS3betaPS), since loss of just one alpha subunit in the midgut results in either a modest delay (alphaPS1) or no effect (alphaPS3). We have also examined the roles of small GTPases in promoting migration of the primordial midgut cells. We find that dominant negative (N17) versions of Rac and Cdc42 cause a very similar defect in migration as loss of integrins, while those of Rho and Ras have no effect. Thus integrins are involved in mediating migration by creating an optimal substratum for adhesion, adhering to that substratum and possibly by activating Rac and Cdc42.

Animals↗

PubMed2004

alpha4beta1- and alpha6beta1-integrins are functional receptors for midkine, a heparin-binding growth factor.

Midkine is a heparin-binding growth factor that promotes the growth, survival, migration and differentiation of various target cells. So far, receptor-type protein tyrosine phosphatase zeta, low-density-lipoprotein-receptor-related protein and anaplastic lymphoma kinase have been identified as receptors for midkine. We found beta1 integrin in midkine-binding proteins from 13-day-old mouse embryos. beta1-Integrin bound to a midkine-agarose column and was eluted mostly with EDTA. Further study revealed that the alpha-subunits capable of binding to midkine were alpha4 and alpha6. Purified alpha4beta1- and alpha6beta1-integrins bound midkine. Anti-alpha4 antibody inhibited the midkine-dependent migration of osteoblastic cells, and anti-alpha6 antibody inhibited the midkine-dependent neurite outgrowth of embryonic neurons. After midkine treatment, tyrosine phosphorylation of paxillin, an integrin-associated molecule, was transiently increased in osteoblastic cells. Therefore, we concluded that alpha4beta1- and alpha6beta1-integrins are functional receptors for midkine. We observed that the low-density-lipoprotein-receptor-related-protein-6 ectodomain was immunoprecipitated with alpha6beta1-integrin and alpha4beta1-integrin. The low-density-lipoprotein-receptor-related-protein-6 ectodomain was also immunoprecipitated with receptor-type protein tyrosine phosphatase zeta. alpha4beta1- and alpha6beta1-Integrins are expected to co-operate with other midkine receptors, possibly in a multimolecular complex that contains other midkine receptors.

Alleles↗