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Results for “Integrin alpha2”

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PubMed2000

Expression of integrin alpha2beta1 in axons and receptive endings of neurons in rat, hairy skin.

Integrin alpha2beta1 has been considered as a mechano-chemical transducer in endothelial and muscle cells. However, little data is available to show whether integrins play a role in the process of mechanical transduction in peripheral mechanosensory neurons. Using immunohistochemistry, we demonstrate that cutaneous neurons express the extracellular matrix (ECM) receptor integrin alpha2beta1. Specifically, we show that integrins alpha2 and beta1 are co-localized with peripherin in the receptive endings of cutaneous neurons in rat, hairy skin. Integrin immunofluorescence was minimal along the axons of large diameter neurons. These results, together with findings by other investigators, provide evidence suggesting that integrin alpha2beta1 may be a linking agent between mechanical stress in the ECM and modulation of the neuronal response of mechanically sensitive neurons.

Animals↗

PubMed2001

Activated T lymphocytes bind in situ to stromal tissue of colon carcinoma but lack adhesion to tumor cells.

It is not entirely clear which adhesion molecules are responsible for the site-directed traffic of T cells within the tumor microenvironment. The present study investigated whether colon carcinoma tissue and normal colon differ in the expression of functionally relevant molecules. In addition, we identified adhesion molecules involved in the binding of activated T cells onto colon carcinoma in situ. Malignant colon epithelium expressed few adhesion receptors, i.e. CD44 (HERMES), CD49b (integrin alpha2) and CD162 (PSGL-1), whereas the stromal compartment within colon carcinoma was positive for numerous binding molecules, e.g. CD44, CD49a (integrin alpha1), CD49e (integrin alpha5), CD51 (integrin alpha(v)), CD54 (ICAM-1), CD99 (MIC2) and CD162. Lymphocytes infiltrating tumor stroma contrasted with lymphocytes within normal colon interstitium by lacking CD28, CD154 (CD40L), CD56 (NCAM) and CD98 (4F2). Normal activated T cells bound to the lymphocyte-rich areas within the stroma of colon carcinoma using CD44, CD50 (ICAM-3), CD99, CD102 (ICAM-2) and CD162 on the T lymphocytes. We conclude that lymphocytes within colon carcinoma stroma may lack several functionally crucial cell surface molecules. We present a panel of adhesion molecules that could mediate the migration of activated T lymphocytes into the stroma of colon carcinoma.

Antigens, CD↗

PubMed2004

Integrin engagement differentially modulates epithelial cell motility by RhoA/ROCK and PAK1.

Integrin-ligand binding regulates tumor cell motility and invasion. Cell migration also involves the Rho GTPases that control the interplay between adhesion receptors and the cytoskeleton. We evaluated how specific extracellular matrix ligands modulate Rho GTPases and control motility of human squamous cell carcinoma cells. On laminin-5 substrates, the epithelial cells rapidly spread and migrated, but on type I collagen the cells spread slowly and showed reduced motility. We found that RhoA activity was suppressed in cells attached to laminin-5 through the alpha3 integrin receptor. In contrast, RhoA was strongly activated in cells bound to type I collagen and this was mediated by the alpha2 integrin. Inhibiting the RhoA pathway by expression of a dominant-negative RhoA mutant or by directly inhibiting ROCK, reduced focal adhesion formation and enhanced cell migration on type I collagen. Cdc42 and Rac and their downstream target PAK1 were activated following adhesion to laminin-5. PAK1 activation induced by laminin-5 was suppressed by expression of a dominant-negative Cdc42. Moreover, constitutively active PAK1 stimulated migration on collagen I substrates. Our results indicate that in squamous epithelial cells, collagen-alpha2beta1 integrin binding activates RhoA, slowing cell locomotion, whereas laminin-5-alpha3beta1 integrin interaction inhibits RhoA and activates PAK1, stimulating cell migration. The data demonstrate that specific ligand-integrin pairs regulate cell motility differentially by selectively modulating activities of Rho GTPases and their effectors.

Adenoviridae↗

PubMed1999

Expression of integrin receptors in the human trabecular meshwork.

PURPOSE: To examine the expression of integrin receptors in the human trabecular meshwork. METHODS: The expression of integrins in human tissues was visualized by immunohistochemical staining using integrin-specific antibodies. Immunoprecipitation was performed after biotin labeling of cell surface proteins. Reverse transcriptase-polymerase chain reaction was used to detect the presence of mRNA species for integrin subunits. RESULTS: Human trabecular meshwork tissues obtained from donors 2 to 65 years old stained positively for integrins alpha1, alpha3, alpha4, alpha5, alpha6, alphav, beta1, beta3, beta4 and beta5. The staining was observed mostly around the edges of trabecular beams in association with trabecular meshwork cells. The staining intensity did not appear to vary with donor age. In addition, immunoprecipitation of tissue extracts revealed the presence of integrin alpha2 and confirmed the absence of beta2. Results from polymerase chain reactions were consistent with these findings. CONCLUSIONS: A spectrum of integrin receptors that may have important roles in the cell-matrix interactions are demonstrated in the human trabecular meshwork. The repertoire identified in tissues is similar to that found in cultured cells except that the beta4 expression in tissues is lost in cultures.

Adult↗

PubMed2001

Platelet polymorphisms in thrombotic disorders.

Plaque rupture and/or endothelial damage lead to exposure of von Willebrand factor (VWF) and collagen which facilitate the adhesion of circulating platelets via glycoprotein (GP) GPIb-IX-V and integrin alpha2 beta1, respectively, to the damaged vessel wall. This process activates the platelets and leads to a conformational change of a second integrin alphaIIb beta3 that facilitates fibrinogen binding and platelet aggregation. Thrombin generated at the blood-plaque interface converts fibrinogen to fibrin, which stabilizes thrombus growth. Therefore, any genetic differences that might alter surface expression or activity of these receptors could influence the risk for adverse outcome as a result of the hemostatic process. In the last five years, there has been a rapid accumulation of literature concerning the relationship between genetic variations in platelet glycoproteins and risk for coronary heart disease. In this study, we have presented a comprehensive review of the impact of platelet receptor polymorphisms and thrombotic risk.

Antigens, Human Platelet↗

PubMed1999

Laminin mediates tethering and spreading of colon cancer cells in physiological shear flow.

Under the physiological shear condition, cultured colon cancer cells bound to laminin (LM), but not to fibronectin or vitronectin. Most of the tethered cells did not roll, but arrested immediately and spread within 10-30 min on LM under the continuous presence of shear flow. The tethering of Colo201 was partially inhibited by monoclonal antibodies (mAbs) to alpha6 integrin and a combination of mAbs to beta1 and beta4 integrins, but not by mAb to 67KD laminin receptor. Some Colo201 cells still tethered at 4 degrees C. This suggests that alpha6beta1 and alpha6beta4 integrins participate in Colo201 tethering on LM, although other non-integrin molecules play roles. In contrast, the spread of Colo201 was effectively inhibited by the mAbs to integrin alpha2, alpha6 and beta1 chains. The effect of anti-alpha2 plus anti-alpha6 mAbs was almost equal to anti-beta1, suggesting that Colo201 cells mainly use alpha2beta1 and alpha6beta1 integrins for spreading on LM. When the cells were perfused on subconfluent endothelial cells (HUVEC) cultured on LM, they did not tether on HUVEC but did on coated LM exposed at intercellular gap area. Immunohistochemistry revealed that LM abundantly existed in the cytosol of human portal and hepatic vein endothelial cells. These data suggest that LM can mediate from tethering to spreading of colon cancer cells under the blood flow and plays an essential role in haematogeneous metastasis.

Antibodies, Monoclonal↗

PubMed2001

Cytoskeletal-induced alterations in the adhesion of HT-1080 fibrosarcoma cells to extracellular matrix.

We have investigated the adhesion of the human fibrosarcoma cell line, HT-1080, transfected with glial fibrillary acidic protein (GFAP) to a variety of extracellular matrix macromolecules (ECM) including collagen type IV, laminin, and fibronectin. The GFAP-transfectants demonstrated altered adhesiveness to extracellular matrix substrates when compared to controls. GFAP-positive, heavy metal-induced fibrosarcoma cells were more adherent to plastic and collagen type IV than were the parental or uninduced cells. In contrast, GFAP-positive fibrosarcoma cells were less adherent to laminin- or fibronectin-coated dishes than controls. Time course adhesion studies over 9 days showed that the heavy metal-induced fibrosarcoma cells progressively became more adherent to collagen type IV and less adherent to laminin- or fibronectin-coated dishes than did uninduced cells. However, with the removal of heavy metal from the medium, the HT-1080 fibrosarcoma cells were restored to their original adhesive potential. By phase microscopy, uninduced and induced HT-1080 cells demonstrated different morphological features and remained viable in an anchorage-dependent fashion on collagen type IV as a substrate. By way of contrast, GFAP-induced HT-1080 cells were not particularly viable in monolayer culture and readily detached from laminin as a substrate. The expression of beta1 integrin in GFAP-positive fibrosarcoma cells was decreased following heavy metal induction by Western blot analyses. In contrast, the expression of alpha2 integrin was increased whereas alpha5 integrin was unchanged in HT-1080 cells following the induction of GFAP. Gelatin zymography showed that 72 kDa collagenase was less expressed in GFAP-induced clones than in controls. Our data suggest that the forced expression of the intermediate filament, GFAP, in HT-1080 cells may modulate cell adhesion to different ECM substrates through alterations in expression of integrins.

Blotting, Western↗

PubMed2001

Platelet receptor polymorphisms and thrombotic risk.

Plaque rupture and/or endothelial damage lead to exposure of von Willebrand factor and collagen which facilitate the adhesion of circulating platelets via glycoprotein Ib-IX-V and the integrin alpha2 beta1, respectively, to the damaged vessel wall. This process activates the platelet and leads to a conformational change of a second integrin alphaIIb beta3 that facilitates fibrinogen binding and platelet aggregation. Thrombin generated at the blood-plaque interface converts fibrinogen to fibrin, which stabilizes thrombus growth. Therefore, any genetic differences that might alter surface expression or activity of these receptors could influence risk for adverse outcomes as a result of the haemostatic process. In the last 5 years, there has been a rapid accumulation of the literature concerning the relationship between genetic variations in platelet glycoproteins and risk for coronary heart disease. In this chapter, we present a comprehensive review of the impact of platelet receptor polymorphisms and thrombotic risk.

Antigens, CD↗

PubMed2000

The ability in adhesion and invasion of drug-resistant human glioma cells.

Drug-resistance is critical in treating malignant tumors, and a variety of treatments are given to control it. Little study has been done, however, on biological changes in tumor cell activity in the course of acquiring drug-resistance. We used a glioma cell line to study changes in cell adhesion and invasion on acquiring drug-resistance. Human glioma culture cell line IN157 was used to establish the cell lines resistant to etoposide (VP-16), vincristine sulfate (VCR), and doxorubicin hydrochloride (DOX). Expressions of integrin alpha2, alpha3, alpha5, and beta1, neuronal cell adhesion molecule (NCAM), and matrix metalloproteinases (MMPs) were examined by flow cytometry. In drug-resistant cells, integrin expression was enhanced and NCAM expression was reduced. Adhesions to the extracellar matrix (ECM) proteins (laminin, fibronectin or type IV collagen) were studied. The adhesive ability of all cell lines increased in a concentration-dependent manner. Adhesion of drug-resistant cells was significantly stronger than that of IN157. The cell invasion of drug-resistant cell lines to the basal membrane was significantly lower than that of IN157. The cell invasion of IN157 was significantly suppressed by adding anti-NCAM antibody. In the case of IN157 with the acquisition of drug-resistance, an increase in the expression of integrins may have enhanced the adhesion to ECM proteins. This finding may be concerned with the decreased activity of drug-resistant cell lines in invading the basement membrane. NCAM expression in drug-resistant cell lines was reduced and anti-NCAM antibody abated invasion of IN157, suggesting that NCAM is involved in IN157 invasion.

Animals↗

PubMed2006

Identification and characterization of triosephosphate isomerase that specifically interacts with the integrin alphaIIb cytoplasmic domain.

Integrin alphaIIb/beta3 (IIb/IIIa), a platelet fibrinogen receptor, has been shown to play a critical role in thrombosis and hemostasis. However, the mechanisms by which ligands interact with the alphaIIb/beta3 receptor is not very clear at this time. The interaction between the ligand, the receptor and the transmission of extracellular signals may involve the cytoplasmic domains of these integrins. The objective of this investigation was to identify novel proteins that interact with the cytoplasmic tail of alphaIIb. Using alphaIIb cytoplasmic tail as the bait and a yeast two-hybrid system, we have identified three separate clones containing inserts that encoded the same protein with different truncated N-terminals. Sequence analysis showed that the inserts of the three clones encoded a previously identified enzyme: triose phosphate isomerase (TPI). In addition, we demonstrated that TPI failed to interact with the integrin alpha2 tail, beta3 tail and lamin, but showed a weak binding to the alphaV tail which shares the highest homology with alphaIIb tail among the integrin alpha family. Site-directed mutagenesis studies around the homology region indicated that the critical peptide sequence necessary for the interaction between TPI and alphaIIb tail is GFFKRNRPPLEE. Using RT-PCR, we have demonstrated the presence of TPI mRNA in platelets. In addition, experiments were also performed to demonstrate specific binding of TPI to alphaIIb using an ELISA and fusion protein. Taken together, these data suggest that TPI specifically interacts with alphaIIb and may play a critical role in alphaIIb/beta3-mediated platelet function.

Amino Acid Sequence↗

PubMed2001

Modulation of alpha2beta1 integrin changes during mammary gland development by beta-oestradiol.

In order to study the role of cell-matrix interactions in mammary gland function, temporal changes in alpha2beta1 integrin, the major receptor for collagen and the influence of beta-oestradiol on its level and distribution in rat mammary gland at different stages of development were studied. The level of alpha2beta1 integrin determined by ELISA, was found to be high during different days of pregnancy, while in the lactating stage, it was significantly reduced. By immunocytochemical analysis, alpha2beta1 integrin was found to be localized towards the luminal side of acinar cells, both in the virgin and midpregnant stage, while it was not detected in the lactating stage. The possible role of hormones in modulating the level of integrin was examined in both in vitro and in vivo experiments using beta-oestradiol. Supplementing beta-oestradiol to isolated mammary epithelial cells from both virgin and lactating glands caused a concentration dependent increase in the incorporation of [35S]methionine into alpha2beta1 integrin associated with the cells. Administration of beta-oestradiol to virgin and lactating glands caused about 1.4-4-fold increase in the level of alpha2 integrin, indicating that upregulation of integrin during pregnancy may be due to oestrogen and as the oestrogen level falls during lactating phase, downregulation of alpha2beta1 integrin occurs. Treatment with beta-oestradiol also resulted in the appearance of alpha2beta1 integrin in the acinar region of the lactating tissue, while in the untreated controls no staining for integrin was seen. These results indicate that oestrogen, apart from directly affecting the cellular activity, can influence mammary tissue function by affecting cell-ECM interactions through the modulation of integrin receptors for matrix proteins.

Animals↗

PubMed2006

Interactions of primary fibroblasts and keratinocytes with extracellular matrix proteins: contribution of alpha2beta1 integrin.

The alpha2beta1 integrin is a collagen-binding protein with very high affinity for collagen I. It also binds several other collagens and laminins and it is expressed by many cells, including keratinocytes and fibroblasts in the skin. In the past, alpha2beta1 integrin was suggested to be responsible for cell attachment, spreading and migration on monomeric collagen I and contraction of three-dimensional collagen lattices. In view of these functions, normal development and fertility in integrin alpha2-deficient mice, which we generated by targeting the integrin alpha2 gene, came as a surprise. This suggested the existence of compensatory mechanisms that we investigate here using primary fibroblasts and keratinocytes isolated from wild-type and alpha2-deficient mice, antibodies blocking integrin function and downregulation of integrin alpha2 expression. The results show that the alpha2beta1 integrin is absolutely required for keratinocyte adhesion to collagens whereas for fibroblasts other collagen-binding integrins partially back-up the lack of alpha2beta1 in simple adhesion to collagen monomers. A prominent requirement for alpha2beta1 integrins became apparent when fibroblasts executed mechanical tasks of high complexity in three-dimensional surroundings, such as contracting free-floating collagen gels and developing isometric forces in tethered lattices. The deficits observed for alpha2-deficient fibroblasts appeared to be linked to alterations in the distribution of force-bearing focal adhesions and deregulation of Rho-GTPase activation.

Animals↗

PubMed2000

Effects of natural product extracts on contraction and mechanical properties of fibroblast populated collagen gel.

Fibroblast-populated collagen gel cultures have been used as a dermal model of wound contraction and granulation in the wound healing process and as an in vitro model of dermal tissue. We evaluated the effects of various natural product extracts on collagen gel contraction-promoting activity and mechanical properties (relaxation time) using this model, and observed that some natural product extracts, such as Hibamata extract (from Fucus vesiculosus) promoted gel contraction and increased the relaxation time of the gels. In addition, we investigated the mechanism of the promotion of the gel contraction, noting increased expression of integrin alpha2 and beta1 subunit molecules on the surface of the fibroblasts, suggesting that some extracts, such as Hibamata extract, promote gel contraction by increasing the expression of integrin molecules on the fibroblasts surface. For other types of natural product extracts, other mechanisms of the gel contraction-promoting activity, which were independent of an increase of integrins, were suggested. Although the mechanisms of promotion of gel contraction by these extracts are still unclear, it is at least clear that, more than one mechanism appears to be present. Therefore, more effective drug regimens for improving dermal tissues and wound healing may be achieved by combining drugs which increase integrin molecules and drugs with other mechanisms of action.

Blotting, Western↗

PubMed1997

Differential motile response of human malignant mesothelioma cells to fibronectin, laminin and collagen type IV: the role of beta1 integrins.

Beta1 integrins are widely expressed in human tissues but their presence and function on malignant mesothelioma cells have not been examined. In this study, we have investigated the expression and function of beta1 integrins in 7 human malignant mesothelioma cell lines. Immunofluorescence staining and FACS analysis showed similar expression of beta1 integrins with strongest expression of alpha3beta1 in all investigated mesothelioma cell lines. Using the Boyden chamber assay, we found that mesothelioma cell lines migrated to soluble (chemotaxis) and substrate-bound (haptotaxis) fibronectin, laminin and collagen type IV. In order to investigate the biological function of integrins in mesothelioma cells, we pre-incubated the cells with blocking anti-integrin monoclonal antibodies (MAbs) prior to the adhesion and migration assays. Anti-beta1 antibodies inhibited cell adhesion, chemotaxis and haptotaxis in all cell lines. Generally, anti-alpha2 integrin antibodies inhibited cell adhesion, chemotactic and haptotactic migration to collagen type IV, whereas antibodies to the alpha5 and alpha6 subunits inhibited cell adhesion and migration to fibronectin and laminin, respectively. Preincubation of mesothelioma cells with anti-alpha3 antibodies inhibited the migration to either collagen type IV, laminin or fibronectin in all cell lines. Interestingly, in 3 cell lines anti-alpha3 antibodies inhibited cell migration to laminin and collagen type IV without affecting the ability of the cells to adhere to these proteins. Furthermore, in 2 cell lines, antibodies to the alpha3 chain inhibited chemotaxis but not haptotaxis to collagen type IV, indicating the presence of distinct signalling pathways.

Antibodies↗

PubMed2000

Activation of the alpha2beta1 integrin prevents c-erbB2-induced scattering and apoptosis of human mammary epithelial cells in collagen.

Constitutive overexpression of c-erbB2 in the mammary epithelial cell line MTSV1-7 has been shown to result in epithelial-mesenchymal conversion, anchorage-independent growth and loss of organized morphogenesis in collagen. To elucidate the events leading to this drastic change, MTSV1-7 cells and its subclone HB2 (which shows a more strictly epithelial phenotype) were transfected with the hybrid trk-neu receptor consisting of the extracellular domain of the trkA nerve growth factor (NGF) receptor and the transmembrane and cytoplasmic domains of c-erbB2 (neu). In cells expressing this construct, c-erbB2 homodimerization can be mimicked by addition of NGF. In trk-neu transfectants of HB2 cells, modest expression led to increased cell proliferation upon NGF treatment. When clones with higher expression levels were grown in collagen, NGF instead induced cell scattering, diminished viability and dramatically increased apoptosis. Interestingly, both the dissociation of colonies and loss of cell viability could be completely reversed by treatment of the cells with antibodies that activate the adhesive capacity of the alpha2beta1 integrin. Long-term NGF treatment of high-expressing transfectants generated fibroblastic clones displaying a reduced expression of integrin alpha2 and E-cadherin, and extensive apoptosis in collagen. These results, which indicate that strong c-erbB2 signalling may lead to downregulation and/or inactivation of the alpha2beta1 integrin, promoting apoptosis in collagen, provide one possible explanation to the increased apoptosis frequently seen in early tumour development.

Antibodies, Monoclonal↗

PubMed2003

The modulation of integrin expression by the extracellular matrix in articular chondrocytes.

Normal articular cartilage is composed of chondrocytes embedded within an extracellular matrix (ECM). The patterns of integrin expression determine the adhesive properties of cells by modulating interactions with specific ECMs. Our hypothesis is that chondrocyte integrin expression changes in response to changes in their microenvironment. Porcine articular chondrocytes were encapsulated in alginate beads with several ECMs (collagen type I, collagen type II and fibronectin) for 7 days, subjected to RT-PCR, western blot analysis and immunofluorescence staining. It was found that chondrocytes in different ECMs showed different patterns of integrin expression. Integrin alpha5 and beta1 were strongly expressed in all groups, but integrin alpha1 was strongly expressed only in collagen type I and fibronectin conjugated alginate beads, and integrin alpha2 was strongly expressed only in collagen type II conjugated alginate beads. These findings suggest that the addition of different ECMs to chondrocytes can modulate the patterns and levels of integrin expression possibly through a feedback mechanism. These finding suggest that the modulation of ECM interactions may play a critical role in the pathogenesis of osteoarthritis.

Animals↗

PubMed2002

The regulation of prostate cancer cell adhesion to human bone marrow endothelial cell monolayers by androgen dihydrotestosterone and cytokines.

A previous study from our laboratory suggested that prostate cancer metastasis to bone may be mediated, in part, by preferential adhesion to human bone marrow endothelial (HBME) cells. Tumor cell adhesion to endothelial cells may be modulated by the effect of cytokines on cell adhesion molecules (CAMs). Tumor necrosis factor-alpha (TNF-alpha) regulates VCAM expression on the endothelium and this effect is enhanced by dihydrotestosterone (DHT). Transforming growth factor-beta (TGF-beta) stimulates the expression of alpha2beta1 integrin on PC-3 cells. The current study investigated the effects of the above cytokines and DHT (singularly and in various combinations) upon HBME and prostate cancer cell expression of VCAM, alpha2 integrin subunit, and beta1 integrin subunit by flow cytometry. We also monitored the effects of the above treatments on PC-3 cell adhesion to HBME monolayers. The data demonstrate that none of the treatments significantly altered the expression of selected CAMs on HBME cell and neoplastic prostate cell lines. The treatment of HBME monolayers with various combinations of cytokines and DHT prior to performing adhesion assays with PC-3 demonstrates that treatments containing TGF-beta reduced PC-3 cell adhesion to HBME monolayers by 32% or greater (P < 0.05). The reduction in PC-3 cell adhesion to TGF-beta-treated HBME monolayers was dose dependent. Interestingly, LNCaP cells but not PC-3 cells treated with TGF-beta had a reduced ability to adhere to untreated HBME monolayers. These results suggest that TGF-beta may reduce tumor cell adhesion to bone marrow microvascular endothelium, in vivo. The biological significance of this observation is discussed.

Adenocarcinoma↗

PubMed2000

alpha5beta1 integrin protects intestinal epithelial cells from apoptosis through a phosphatidylinositol 3-kinase and protein kinase B-dependent pathway.

Renewal of the gastrointestinal epithelium involves a coordinated process of terminal differentiation and programmed cell death. Integrins have been implicated in the control of apoptotic processes in various cell types. Here we examine the role of integrins in the regulation of apoptosis in gastrointestinal epithelial cells with the use of a rat small intestinal epithelial cell line (RIE1) as a model. Overexpression of the integrin alpha5 subunit in RIE1 cells conferred protection against several proapoptotic stimuli. In contrast, overexpression of the integrin alpha2 subunit had no effect on cell survival. The antiapoptotic effect of the alpha5 subunit was partially retained by a mutated version that had a truncation of the cytoplasmic domain. The antiapoptotic effects of the full-length or truncated alpha5 subunit were reversed upon treatment with inhibitors of phosphatidylinositol 3-kinase (PI-3-kinase), suggesting that the alpha5beta1 integrin might interact with the PI-3-kinase/Akt survival pathway. When cells overexpressing alpha5 were allowed to adhere to fibronectin, there was a moderate activation of protein kinase B (PKB)/Akt, whereas no such effect was seen in alpha2-overexpressing cells adhering to collagen. Furthermore, in cells overexpressing alpha5 and adhering to fibronectin, there was a dramatic enhancement of the ability of growth factors to stimulate PKB/Akt; again, this was not seen in cells overexpressing alpha2 subunit and adhering to collagen or fibronectin. Expression of a dominant negative version of PKB/Akt in RIE cells blocked to ability of alpha5 to enhance cell survival. Thus, the alpha5beta1 integrin seems to protect intestinal epithelial cells against proapoptotic stimuli by selectively enhancing the activity of the PI-3-kinase/Akt survival pathway.

Animals↗