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Results for “Integrin beta1”

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PubMed1999

Laminin and beta1 integrins are crucial for normal mammary gland development in the mouse.

We have examined the role of integrin-extracellular matrix interactions in the morphogenesis of ductal structures in vivo using the developing mouse mammary gland as a model. At puberty, ductal growth from terminal end buds results in an arborescent network that eventually fills the gland, whereupon the buds shrink in size and become mitotically inactive. End buds are surrounded by a basement membrane, which we show contains laminin-1 and collagen IV. To address the role of cell-matrix interactions in gland development, pellets containing function-perturbing anti-beta1 integrin, anti-alpha6 integrin, and anti-laminin antibodies respectively were implanted into mammary glands at puberty. Blocking beta1 integrins dramatically reduced both the number of end buds per gland and the extent of the mammary ductal network, compared with controls. These effects were specific to the end buds since the rest of the gland architecture remained intact. Reduced development was still apparent after 6 days, but end buds subsequently reappeared, indicating that the inhibition of beta1 integrins was reversible. Similar results were obtained with anti-laminin antibodies. In contrast, no effect on morphogenesis in vivo was seen with anti-alpha6 integrin antibody, suggesting that alpha6 is not the important partner for beta1 in this system. The studies with beta1 integrin were confirmed in a culture model of ductal morphogenesis, where we show that hepatocyte growth factor (HGF)-induced tubulogenesis is dependent on functional beta1 integrins. Thus integrins and HGF cooperate to regulate ductal morphogenesis. We propose that both laminin and beta1 integrins are required to permit cellular traction through the stromal matrix and are therefore essential for maintaining end bud structure and function in normal pubertal mammary gland development.

Animals↗
PubMed2006

Identification of multiple integrin beta1 homologs in zebrafish (Danio rerio).

BACKGROUND: Integrins comprise a large family of alpha,beta heterodimeric, transmembrane cell adhesion receptors that mediate diverse essential biological functions. Higher vertebrates possess a single beta1 gene, and the beta1 subunit associates with a large number of alpha subunits to form the major class of extracellular matrix (ECM) receptors. Despite the fact that the zebrafish (Danio rerio) is a rapidly emerging model organism of choice for developmental biology and for models of human disease, little is currently known about beta1 integrin sequences and functions in this organism. RESULTS: Using RT-PCR, complete coding sequences of zebrafish beta1 paralogs were obtained from zebrafish embryos or adult tissues. The results show that zebrafish possess two beta1 paralogs (beta1-1 and beta1-2) that have a high degree of identity to other vertebrate beta1 subunits. In addition, a third, more divergent, beta1 paralog is present (beta1-3), which may have altered ligand-binding properties. Zebrafish also have other divergent beta1-like transcripts, which are C-terminally truncated forms lacking the transmembrane and cytoplasmic domains. Together with beta1-3 these truncated forms comprise a novel group of beta1 paralogs, all of which have a mutation in the ADMIDAS cation-binding site. Phylogenetic and genomic analyses indicate that the duplication that gave rise to beta1-1 and beta1-2 occurred after the divergence of the tetrapod and fish lineages, while a subsequent duplication of the ancestor of beta1-2 may have given rise to beta1-3 and an ancestral truncated paralog. A very recent tandem duplication of the truncated beta1 paralogs appears to have taken place. The different zebrafish beta1 paralogs have varied patterns of temporal expression during development. Beta1-1 and beta1-2 are ubiquitously expressed in adult tissues, whereas the other beta1 paralogs generally show more restricted patterns of expression. CONCLUSION: Zebrafish have a large set of integrin beta1 paralogs. beta1-1 and beta1-2 may share the roles of the solitary beta1 subunit found in other vertebrates, whereas beta1-3 and the truncated beta1 paralogs may have acquired novel functions.

Amino Acid Sequence↗
PubMed2004

Variant glycosylation: an underappreciated regulatory mechanism for beta1 integrins.

Although it has been known for many years that beta1 integrins undergo differential glycosylation in accordance with changes in cell phenotype, the potential role of N-glycosylation as a modulator of integrin function has received little attention. One reason for the relatively limited interest in this topic likely relates to the fact that much of the prior research was correlative in nature. However, new results now bolster the hypothesis that there is a causal relationship between variant glycosylation and altered integrin activity. In this review, the evidence for variant glycosylation as a regulatory mechanism for beta1 integrins are summarized, with particular emphasis on: (1). outlining the instances in which cell phenotypic variation is associated with differential beta1 glycosylation, (2). describing the specific alterations in glycan structure that accompany phenotypic changes and (3). presenting potential mechanisms by which variant glycosylation might regulate integrin function.

Animals↗
PubMed2006

[Effects of rosiglitazone on the expression of beta1, integrin and ICAM-1 in high glucose-induced rat glomerular mesangial cells].

OBJECTIVE: To observe the effects of PPARgamma activators thiazolidinediones (Rosiglitazone) on the expression of intercellular adhesion molecule-1 (ICAM-1) and beta1 integrin in high glucose-induced rat glomerular mesangial cells (GMC) in order to elucidate the relationship between PPARgamma and adhesion molecules. METHODS: Rat HBZY-1 GMCs were cultured in vitro and divided into 9 groups: Normal Glucose group (N), High Glucose group (H), Mannitiol group (M), Normal and High Glucose plus 1, 5, 10 micromol/L Rosiglitazone. Every group was treated for 24 hours. The expression of ICAM-1 was measured by immunohistochemistry, the expression of beta1 integrin by indirect immunofluorescence staining and flow cytometry. RESULTS: It was found that high glucose can significantly increase the expression of ICAM-1 and beta1 integrin in GMCs, which is independent of the osmotic pressure. Rosiglitazone can inhibit the expression of ICAM-1 and beta1 integrin in normal and high glucose treated GMCs, and the inhibition is stronger in high glucose treated-group, which is in a dose-dependent manner. The expression of beta1 integrin is positively correlated with ICAM-1. CONCLUSION: Adhesion molecules involves in the pathogenesis of diabetic nephropathy (DN). PPARgamma activators-Rosiglitazone may exert effect on mesangial expansion and glomerulosclerosis in DN through the inhibition of expressions of adhesion molecules induced by high glucose.

Animals↗
PubMed2006

Genetic analysis of beta1 integrin "activation motifs" in mice.

Akey feature of integrins is their ability to regulate the affinity for ligands, a process termed integrin activation. The final step in integrin activation is talin binding to the NPXY motif of the integrin beta cytoplasmic domains. Talin binding disrupts the salt bridge between the alpha/beta tails, leading to tail separation and integrin activation. We analyzed mice in which we mutated the tyrosines of the beta1 tail and the membrane-proximal aspartic acid required for the salt bridge. Tyrosine-to-alanine substitutions abolished beta1 integrin functions and led to a beta1 integrin-null phenotype in vivo. Surprisingly, neither the substitution of the tyrosines with phenylalanine nor the aspartic acid with alanine resulted in an obvious defect. 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.

Alanine↗
PubMed2004

Syk tyrosine kinase participates in beta1-integrin signaling and inflammatory responses in airway epithelial cells.

The protein tyrosine kinase Syk is critically involved in immunoreceptor signaling in hematopoietic cells. Recent studies demonstrate Syk expression in nonhematopoietic cells, including fibroblasts, endothelial cells, hepatocytes, and breast epithelium. However, the role of Syk in these cells is uncertain. We hypothesized that Syk is expressed in respiratory epithelial cells (EC) and that it functions as a signaling molecule involved in inflammatory responses in the epithelium. With the use of immunohistochemistry, Western blot, PCR, and laser scanning confocal microscopy, Syk was detected in human, rat, and mouse bronchial epithelium in situ and in cultured human bronchial EC in primary cells and the cell lines HS-24 and BEAS-2B. Syk-dependent signaling pathways in EC were initiated by engagement of beta1-integrin receptors. Stimulation of beta1-integrin receptors by fibronectin or antibody cross-linking caused redistribution of Syk from a cytoplasmic to plasma membrane localization. In stimulated cells, Syk and beta1-integrin colocalized. In addition, following beta1-integrin receptor engagement, tyrosine phosphorylation of Syk was observed. Expression of the intercellular adhesion molecule-1 (ICAM-1) and production of IL-6, both important molecules in lung inflammation, was downregulated in EC treated with Syk small interfering RNA or Syk inhibitor piceatannol. We propose that Syk is involved in signaling pathways induced by integrin engagement in airway EC. Syk-mediated signaling regulates IL-6 and ICAM-1 expression and may be important in the pathophysiology of lung inflammation.

Animals↗
PubMed2006

The Arf6 GEF GEP100/BRAG2 regulates cell adhesion by controlling endocytosis of beta1 integrins.

The small GTPase Arf6 has been shown to regulate the post-endocytic trafficking of a subset of membrane proteins, including beta1 integrins, and inhibition of Arf6 function impairs both cell adhesion and motility. The activity of Arf GTPases is regulated by a large family of guanine nucleotide exchange factors (GEFs). Arf-GEP100/BRAG2 is a GEF with reported specificity for Arf6 in vitro, but it is otherwise poorly characterized. Here we report that BRAG2 exists in two ubiquitously expressed isoforms, which we call BRAG2a and BRAG2b, both of which can activate Arf6 in vivo. Depletion of endogenous BRAG2 by siRNA leads to dramatic effects in the cell periphery; one such effect is an accumulation of beta1 integrin on the cell surface and a corresponding enhancement of cell attachment and spreading on fibronectin-coated substrates. In contrast, depletion of Arf6 leads to intracellular accumulation of beta1 integrin and reduced adhesion and spreading. These findings suggest that Arf6 regulates both endocytosis and recycling of beta1 integrins and that BRAG2 functions selectively to activate Arf6 during integrin internalization.

ADP-Ribosylation Factor 6↗
PubMed2003

Decreased expression of keratinocyte beta1 integrins in chronically sun-exposed skin in vivo.

BACKGROUND: Chronic exposure to ultraviolet (UV) radiation induces changes in the skin structure which are mostly found in the superficial dermis and at the dermal-epidermal junction. Keratinocytes and fibroblasts contribute both to the synthesis and to the degradation of the molecules important for the integrity of this skin site. While several studies have reported on alterations of dermal components and of the functions of fibroblasts in vivo and in vitro after UV exposure, recent data suggested that keratinocytes could be the main skin cell type involved in the photoageing process. OBJECTIVES: In this study, we analysed the expression of two keratinocyte molecules namely, beta1 integrin (a proliferation marker) and involucrin (a differentiation marker) in sun-exposed and sun-protected facial skin of 16 healthy patients undergoing facial lifting. METHODS: Methods included histology, immunohistochemistry and quantitative reverse transcriptase-polymerase chain reaction analysis. RESULTS: Sun-exposed skin displayed the characteristic morphological and molecular features of dermal photoageing, compared with sun-protected skin, including dermal elastosis, diminished fibrillin and type VII collagen expression. Analysis of the epidermis in sun-exposed vs. sun-protected skin showed no histological differences, but dramatic changes in the expression of beta1 integrin and involucrin. In sun-exposed skin, expression of beta1 integrin protein by epidermal basal cells was reduced, paralleling a downregulation of beta1 integrin mRNA, whereas involucrin protein expression was greatly enhanced in the superficial epidermal cell layers. Interestingly, the ratio between involucrin and beta1 integrin protein expression was consistently increased in sun-exposed skin sites. CONCLUSIONS: Collectively these results demonstrate that epidermal homeostasis is impaired by chronic UV exposure, and define beta1 integrin expression as a molecular marker of the epidermal photoageing process.

Aged↗
PubMed1998

Stimulation of IRS-1-associated phosphatidylinositol 3-kinase and Akt/protein kinase B but not glucose transport by beta1-integrin signaling in rat adipocytes.

The signal transduction pathway by which insulin stimulates glucose transport is not understood, but a role for complexes of insulin receptor substrate (IRS) proteins and phosphatidylinositol (PI) 3-kinase as well as for Akt/protein kinase B (PKB) has been proposed. Here, we present evidence suggesting that formation of IRS-1/PI 3-kinase complexes and Akt/PKB activation are insufficient to stimulate glucose transport in rat adipocytes. Cross-linking of beta1-integrin on the surface of rat adipocytes by anti-beta1-integrin antibody and fibronectin was found to cause greater IRS-1 tyrosine phosphorylation, IRS-1-associated PI 3-kinase activity, and Akt/PKB activation, detected by anti-serine 473 antibody, than did 1 nM insulin. Clustering of beta1-integrin also significantly potentiated stimulation of insulin receptor and IRS-1 tyrosine phosphorylation, IRS-associated PI 3-kinase activity, and Akt/PKB activation caused by submaximal concentrations of insulin. In contrast, beta1-integrin clustering caused neither a change in deoxyglucose transport nor an effect on the ability of insulin to stimulate deoxyglucose uptake at any concentration along the entire dose-response relationship range. The data suggest that (i) beta1-integrins can engage tyrosine kinase signaling pathways in isolated fat cells, potentially regulating fat cell functions and (ii) either formation of IRS-1/PI 3-kinase complexes and Akt/PKB activation is not necessary for regulation of glucose transport in fat cells or an additional signaling pathway is required.

Adipocytes↗
PubMed2001

Mechanisms of chondrocyte adhesion to cartilage: role of beta1-integrins, CD44, and annexin V.

The initial adhesion of transplanted chondrocytes to surrounding host cartilage may be important in the repair of articular defects. Adhesion may position cells to secrete molecules that fill the defect and integrate repair tissue with host tissue. While chondrocytes are known to become increasingly adherent to cartilage with time, the molecular basis for this is unknown. The objective of this study was to investigate the role of beta1-integrin, CD44, and annexin V receptors in chondrocyte adhesion to cartilage. Chondrocytes were cultured in high density monolayer, released with trypsin, and allowed to recover in suspension for 2 h at 37 degrees C. Under these conditions, flow cytometry analysis showed that chondrocytes expressed beta1-integrins, CD44, and annexin V. In a rapid screening assay to assess chondrocyte adhesion to cartilage, cell detachment decreased from 79% at 10 min following transplantation to 10% at 320 min. Treatment of cells with a monoclonal antibody to block beta1-integrins significantly increased chondrocyte detachment from cartilage compared to untreated controls. Similarly, results from a parallel-plate shear flow adhesion assay showed that blocking beta1-integrins significantly increased chondrocyte detachment from cartilage compared to untreated controls at each level of applied shear (0-70 Pa). In both assays, treatment of cells with reagents that block CD44 (hyaluronan oligosaccharides or monoclonal Ab IM7) or annexin V (polyclonal Ab #8958) had no detectable effect on adhesion. With cartilage treated with chondroitinase ABC, blocking beta1-integrins also increased chondrocyte detachment, while blocking CD44 and annexin V also had no detectable effect. Under the conditions studied here, beta1-integrins appear to mediate chondrocyte adhesion to a cut cartilage surface. Delineation of the mechanisms of adhesion may have clinical implications by allowing cell manipulations or matrix treatments to enhance chondrocyte adhesion and retention at a defect site.

Animals↗
PubMed2004

Targeted disruption of beta1-integrin in a transgenic mouse model of human breast cancer reveals an essential role in mammary tumor induction.

Despite evidence demonstrating the role of beta1-integrin in the regulation of cancer cell proliferation in vitro, the importance of this cell adhesion receptor during the initiation and progression of epithelial tumors in vivo remains unclear. Here we have used the Cre/LoxP1 recombination system to disrupt beta1-integrin function in the mammary epithelium of a transgenic mouse model of human breast cancer. Using this approach, we show that beta1-integrin expression is critical for the initiation of mammary tumorigenesis in vivo, and for maintaining the proliferative capacity of late-stage tumor cells. These observations provide a direct demonstration that beta1-integrin plays a critical role in both the initiation and maintenance of mammary tumor growth in vivo.

Animals↗
PubMed2001

Abnormal growth factor modulation of beta1-integrin-mediated adhesion in chronic myelogenous leukaemia haematopoietic progenitors.

Abnormal progenitor circulation and extramedullary haematopoiesis are characteristic features of chronic myelogenous leukaemia (CML). Growth factor (GF) and beta1-integrin interactions play an important role in regulation of progenitor trafficking to and from the marrow space. CML progenitors demonstrate abnormal beta1-integrin-mediated adhesion to fibronectin (FN). In the present study we investigated whether GF modulation of beta1-integrin-mediated adhesion and migration was altered in CML progenitors. Culture with low concentrations of GF enhanced normal progenitor adhesion to FN compared with no GF, but failed to enhance CML progenitor adhesion to FN. Similarly, high concentrations of selected GF rapidly enhanced beta1-integrin-mediated adhesion of normal progenitors to FN through a phosphotidylinositol-3 (PI-3) kinase-dependent mechanism, but failed to increase CML progenitor adhesion. Exposure to a BCR-ABL tyrosine kinase inhibitor restored GF modulation of CML progenitor adhesion. CML colony-forming cells (CFC) demonstrated increased migration across FN-coated transwells compared with normal CFC in the absence of GF. The addition of stem cell factor resulted in enhanced migration of CML and normal CFC on FN. In conclusion, GF stimulation failed to enhance integrin-mediated adhesion but enhanced migration in CML progenitors on FN. BCR-ABL induced abnormalities in GF-integrin interactions could contribute to abnormal circulation and microenvironmental localization of CML progenitors.

Androstadienes↗
PubMed2005

Ablation of beta1 integrin in mammary epithelium reveals a key role for integrin in glandular morphogenesis and differentiation.

Integrin-mediated adhesion regulates the development and function of a range of tissues; however, little is known about its role in glandular epithelium. To assess the contribution of beta1 integrin, we conditionally deleted its gene in luminal epithelia during different stages of mouse mammary gland development and in cultured primary mammary epithelia. Loss of beta1 integrin in vivo resulted in impaired alveologenesis and lactation. Cultured beta1 integrin-null cells displayed abnormal focal adhesion function and signal transduction and could not form or maintain polarized acini. In vivo, epithelial cells became detached from the extracellular matrix but remained associated with each other and did not undergo overt apoptosis. beta1 integrin-null mammary epithelial cells did not differentiate in response to prolactin stimulation because of defective Stat5 activation. In mice where beta1 integrin was deleted after the initiation of differentiation, fewer defects in alveolar morphology occurred, yet major deficiencies were also observed in milk protein and milk fat production and Stat5 activation, indicating a permissive role for beta1 integrins in prolactin signaling. This study demonstrates that beta1 integrin is critical for the alveolar morphogenesis of a glandular epithelium and for maintenance of its differentiated function. Moreover, it provides genetic evidence for the cooperation between integrin and cytokine signaling pathways.

Animals↗
PubMed2000

The nonreceptor tyrosine kinase fer mediates cross-talk between N-cadherin and beta1-integrins.

Cadherins and integrins must function in a coordinated manner to effectively mediate the cellular interactions essential for development. We hypothesized that exchange of proteins associated with their cytoplasmic domains may play a role in coordinating function. To test this idea, we used Trojan peptides to introduce into cells and tissues peptide sequences designed to compete for the interaction of specific effectors with the cytoplasmic domain of N-cadherin, and assayed their effect on cadherin- and integrin-mediated adhesion and neurite outgrowth. We show that a peptide mimicking the juxtamembrane (JMP) region of the cytoplasmic domain of N-cadherin results in inhibition of N-cadherin and beta1-integrin function. The effect of JMP on beta1-integrin function depends on the expression of N-cadherin and is independent of transcription or translation. Treatment of cells with JMP results in the release of the nonreceptor tyrosine kinase Fer from the cadherin complex and its accumulation in the integrin complex. A peptide that mimics the first coiled-coil domain of Fer prevents Fer accumulation in the integrin complex and reverses the inhibitory effect of JMP. These findings suggest a new mechanism through which N-cadherin and beta1-integrins are coordinately regulated: loss of an effector from the cytoplasmic domain of N-cadherin and gain of that effector by the beta1-integrin complex.

Amino Acid Sequence↗
PubMed1999

Modulation of TCR signaling by beta1 integrins: role of the tyrosine phosphatase SHP-1.

When cross-linked, beta1 integrins co-activate T cells together with a TCR-CD3 signal. Soluble anti-beta1 monoclonal antibodies, however, inhibit T cell activation. We report inhibition of early tyrosine kinases, including ZAP-70, p59(fyn), CD4-associated p56(lck) and TCR components under this condition. The tyrosine phosphatase SHP-1 is activated by engagement of beta1 integrins and is implicated in this negative regulation since no inhibition occurs in SHP-1 dominant-negative T cells. As shown by the use of Lck-deficient cells, the activation of the protein tyrosine phosphatase depends on a pool of p56(lck) that is not associated with CD4. These cross-talk events were also observed with the alpha4beta1 integrin ligand, VCAM-1. We propose that these results may be important in terms of lymphocyte circulation; while T cells migrate through the vascular endothelium, they are primed for an amplified response; as inflammation develops, a local accumulation of soluble integrin ligands may help to turn it off.

CD3 Complex↗
PubMed1999

Differential regulation of beta1 integrins by chemoattractants regulates neutrophil migration through fibrin.

Chemoattractants differ in their capacity to stimulate neutrophils to adhere to and to migrate through matrices containing fibrin. Formyl methionyl leucyl phenylalanine (fMLP) stimulates neutrophils to adhere closely to, but not to migrate into, fibrin gels. Leukotriene B4 (LTB4) stimulates neutrophils to adhere loosely to and to migrate through fibrin gels. We report that alpha5beta1 integrins regulate the different migratory behaviors on fibrin gels of neutrophils in response to these chemoattractants. fMLP, but not LTB4, activated neutrophil beta1 integrins, as measured by binding of mAb 15/7 to an activation epitope on the beta1 integrins. Antibodies or peptides that block alpha5beta1 integrins prevented fMLP-stimulated neutrophils from forming zones of close apposition on fibrin and reversed fMLP's inhibitory effect on neutrophil chemotaxis through fibrin. In contrast, neither peptides nor antibodies that block beta1 integrins affected the capacity of LTB4-stimulated neutrophils to form zones of loose apposition or to migrate through fibrin gels. These results suggest that chemoattractants generate at least two different messages that direct neutrophils, and perhaps other leukocytes, to accumulate at specific anatomic sites: a general message that induces neutrophils to crawl and a specific message that prepares neutrophils to stop when they contact appropriate matrix proteins for activated beta1 integrins.

Antibodies↗
PubMed2001

Urokinase receptors promote beta1 integrin function through interactions with integrin alpha3beta1.

The urokinase receptor (uPAR) is linked to cellular migration through its capacity to promote pericellular proteolysis, regulate integrin function, and mediate cell signaling in response to urokinase (uPA) binding. The mechanisms for these activities remain incompletely defined, although uPAR was recently identified as a cis-acting ligand for the beta2 integrin CD11b/CD18 (Mac-1). Here we show that a major beta1 integrin partner for uPAR/uPA signaling is alpha3. In uPAR-transfected 293 cells uPAR complexed (>90%) with alpha3beta1 and antibodies to alpha3 blocked uPAR-dependent vitronectin (Vn) adhesion. Soluble uPAR bound to recombinant alpha3beta1 in a uPA-dependent manner (K(d) < 20 nM) and binding was blocked by a 17-mer alpha3beta1 integrin peptide (alpha325) homologous to the CD11b uPAR-binding site. uPAR colocalized with alpha3beta1 in MDA-MB-231 cells and uPA (1 nM) enhanced spreading and focal adhesion kinase phosphorylation on fibronectin (Fn) or collagen type I (Col) in a pertussis toxin- and alpha325-sensitive manner. A critical role of alpha3beta1 in uPA signaling was verified by studies of epithelial cells from alpha3-deficient mice. Thus, uPAR preferentially complexes with alpha3beta1, promoting direct (Vn) and indirect (Fn, Col) pathways of cell adhesion, the latter a heterotrimeric G protein-dependent mechanism of signaling between alpha3beta1 and other beta1 integrins.

Binding Sites↗
PubMed2003

S-phase delay in human hepatocellular carcinoma cells induced by overexpression of integrin beta1.

AIM: To clarify the mechanisms of integrin overexpression in negatively regulating the cell cycle control of hepatocellular carcinoma cells SMMC-7721. METHODS: The cell cycle pattern was determined by flow cytometry. The mRNA and protein expression levels were assayed by RT-PCR and Western blot, respectively. Stable transfection was performed by Lipofectamine 2000 reagent, and cells were screened by G418. RESULTS: Overexpression of alpha5beta1 or beta1 integrin induced S-phase delay in SMMC-7721 cells, and this delay was possibly due to the accumulation of cyclin-dependent kinase inhibitors (CKIs) p21(cip1) and p27(kip1). The decrease of protein kinase B (PKB) phosphorylation was present in this signaling pathway, but focal adhesion kinase (FAK) was not involved. When phosphorylation of PKB was solely blocked by wortmannin, p27(kip1) protein level was increased. Moreover, S-phase delay was recurred when attachment of the parental SMMC-7721 cells was inhibited by the preparation of poly-HEME, and this cell cycle pattern was similar to that of beta1-7721 or alpha5beta1-7721 cells. CONCLUSION: S-phase delay induced by overexpression of integrin beta1 subunit is attributed to the decrease of PKB phosphorylation and subsequent increases of p21(cip1) and p27(kip1) proteins, and may be involved in the unoccupied alpha5beta1 because of lack of its ligands.

Carcinoma, Hepatocellular↗