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Biomedical subjects

R H Kramer

Publications and source records attributed to R H Kramer.

At least 55 records · Page 3Linked to original sources
PubMed1995

Transforming growth factor beta 1 inhibits fetal lamb ductus arteriosus smooth muscle cell migration.

Anatomical closure of the ductus arteriosus (DA) requires normally quiescent smooth muscle cells (SMC) to migrate out of the muscle media into the subendothelial space, forming intimal mounds that eventually coalesce to occlude the vessel's lumen. Transforming growth factor-beta 1 (TGF beta 1), a potent modulator of vascular SMC migration, is found in the wall of the closing DA. We examined the effect of TGF beta 1 on the migration of fetal lamb DA-SMC. Although TGF beta 1 has been shown to be a chemoattractant for other mesenchymal cells, it had no chemotactic effect on DA-SMC; furthermore, TGF beta 1 did not enhance the migration of DA-SMC (as has been reported for aortic SMC). Rather, incubating DA-SMC with TGF beta 1 for 22 h decreased the rate of migration of SMC on extracellular matrix substrata composed of fibronectin, vitronectin, laminin, and collagen I and IV. Exposure of DA-SMC to TGF beta 1 was associated with an increase in the formation of focal adhesion plaques (tight associations between the cells' surface and extracellular matrix). DA-SMC use integrin receptors to attach to and migrate on extracellular matrix components. The decrease in DA-SMC migration was not associated with a significant change in the profile of integrin receptors expressed by the cell. TGF beta 1 had little effect on overall DA-SMC integrin expression, except for a modest increase in the fibronectin receptor (alpha 5 beta 1 integrin). Rather, the decrease in migration and changes in cell morphology were associated with an increased ability of integrin receptors to associate with the cytoskeleton. TGF beta 1 appears to anchor the cell's cytoskeleton to the extracellular matrix, making the cells more adherent and less capable of migrating.

Animals↗
PubMed1994

Hepatocyte growth factor/scatter factor induces tyrosine phosphorylation of focal adhesion kinase (p125FAK) and promotes migration and invasion by oral squamous cell carcinoma cells.

Fibroblasts or their conditioned medium stimulated invasion by squamous cell carcinoma cells. The fibroblast-derived activity responsible for increased invasion is the hepatocyte growth factor/scatter factor (HGF/SF), a ligand for the c-Met receptor. HGF/SF stimulated migration of the cells on various extracellular matrix substrates but did not alter their adhesion efficiency nor integrin expression. HGF/SF stimulated motility in a two step process: initially cells spread rapidly and formed focal adhesions, and then they disassembled these condensations, which was followed by increased cell locomotion. The focal adhesions contained vinculin, p125FAK, beta 1 integrin, and phosphotyrosine. Within minutes after exposure of cells to HGF/SF, proteins of 125 and 145 kDa showed elevated tyrosine phosphorylation and were identified as p125FAK and c-Met, respectively. Gradual loss of tyrosine phosphorylation coincided with disruption of focal adhesions and conversion to a motile phenotype. HGF/SF-mediated tyrosine phosphorylation of p125FAK was inhibited by the tyrosine kinase inhibitor, herbimycin A, which also blocked spreading and the migratory response. These results indicate that fibroblast-derived HGF/SF triggers migration through the initial recruiting of integrins, cytoskeletal proteins, and p125FAK into focal adhesions that is dependent on tyrosine kinase activity.

Benzoquinones↗
PubMed1994

Vitronectin-driven human keratinocyte locomotion is mediated by the alpha v beta 5 integrin receptor.

Vitronectin is a soluble serum factor that is known to promote epiboly of keratinocytes in explant cultures and enhance cell spreading and attachment to matrix. Recently, vitronectin was demonstrated to promote human keratinocyte locomotion. The mechanism(s) by which vitronectin enhances keratinocyte migration is unknown. In this study, we quantitated the vitronectin-driven migration of human keratinocytes in the presence of antibodies to vitronectin receptors. We found that vitronectin's effect of promoting human keratinocyte migration was inhibited by antibody-directed against the alpha v beta 5 receptor. In addition, we surface-labeled human keratinocytes, chromatographed extracts of the cell membranes on a vitronectin column, and then immunoprecipitated the bound and eluted proteins with antibodies to specific vitronectin receptors. We identified the vitronectin receptors on human keratinocytes as bands of 150,000 and 100,000 daltons without reduction and as 125,000 and 110,000 daltons under reducing conditions. Immunoprecipitation with specific antibodies identified the major receptor to be the alpha v beta 5 integrin. In addition, we quantitated vitronectin-driven migration of human keratinocytes in the presence of Arg-Gly-Asp (RGD) and control peptides. We found that the presence of RGD, but not control peptide, inhibited vitronectin-driven migration of human keratinocytes. These studies demonstrate that human keratinocytes express vitronectin receptors and use the alpha v beta 5 receptor for cellular locomotion.

Antibodies↗
PubMed1994

Identification of the high affinity binding site of transforming growth factor-alpha (TGF-alpha) for the chicken epidermal growth factor (EGF) receptor using EGF/TGF-alpha chimeras.

Human epidermal growth factor (hEGF) and human transforming growth factor-alpha (hTGF-alpha) are structurally related growth factors that share relatively little sequence homology. They both exert their biological action by binding to the cell-surface EGF receptor. hEGF and hTGF-alpha bind with similar affinity to the hEGF receptor, but hEGF binds with an approximately 100-fold lower affinity to the chicken EGF receptor compared with hTGF-alpha. To map the region in hTGF-alpha that confers its ability to bind with high affinity to the chicken EGF receptor, 10 hybrids of hEGF and hTGF-alpha were constructed by exchanging domains bordered by the third, fourth, and sixth conserved cysteine residues. The activity of the expressed chimeric proteins was determined by their ability to compete with 125I-labeled mouse EGF for binding to NIH-3T3 cells transfected with the hEGF receptor. Subsequent binding competition studies of NIH-3T3 cells transfected with the chicken EGF receptor showed that chimeras carrying TGF-alpha sequences COOH-terminal of the sixth cysteine have a high affinity for this receptor, similar to hTGF-alpha. In contrast, chimeras with EGF sequences in this COOH-terminal domain have only low binding affinity, similar to hEGF. We conclude that the COOH-terminal linear region of hTGF-alpha is important for its high affinity interaction with the chicken EGF receptor.

Animals↗
PubMed1994

Selective down-regulation of integrin receptors in spheroids of squamous cell carcinoma.

Integrin expression in squamous cell carcinomas have been reported to be down-regulated in vivo. Because integrins are molecules whose functions include the reorganization of cytoskeleton in response to the surrounding extracellular matrix, we have examined the expression of integrins in the transformed cell line A431 when grown as multicellular spheroids or as monolayers. The spheroids were grown to sizes of approximately 100 microns and approximately 600 microns. Since larger A431 spheroids require epidermal growth factor for growth, we also investigated the effect of this growth factor on the expression of integrins in cells grown as monolayers or as small spheroids. Immunostaining studies using monoclonal antibodies specific for alpha 6, beta 1, and beta 4 subunits revealed a strong staining pattern in the periphery of the spheroids. The interior cells of the spheroids showed a moderate, positive reaction with the beta 1 antibody but significantly reduced from that at the periphery. Anti-alpha 2 antibody, on the other hand, revealed a uniform staining around the cells throughout the spheroids. Western blot analyses confirmed an overall diminution of alpha 6 and beta 1 protein levels in the spheroids compared with monolayers. Northern blot analyses showed that the low expression of integrin subunits alpha 6, beta 1, and beta 4 in spheroids was due to a reduction in mRNA transcripts. Northern blot analyses, however, showed no significant change in the expressions of alpha 2, alpha 5, or beta 5 mRNA. Conversely, the expression of alpha v was slightly reduced in spheroids. Epidermal growth factor increased the mRNA expression of alpha 2, alpha 6, beta 1, and beta 4 integrin subunits in cells grown either as monolayers or as spheroids whereas epidermal growth factor had no detectable effect on the expression of alpha v or beta 5. These results mimic the pattern of expression found in vivo and indicate that cell-cell contact and the microenvironments of cells within a spheroid regulate the expression and distribution of a subset of integrin molecules.

Animals↗
PubMed1994

Effects of caffeine on intracellular calcium, calcium current and calcium-dependent potassium current in anterior pituitary GH3 cells.

Caffeine elicits physiological responses in a variety of cell types by triggering the mobilization of Ca2+ from intracellular organelles. Here we investigate the effects of caffeine on intracellular Ca2+ concentration ([Ca2+]i) and ionic currents in anterior pituitary cells (GH3) cells. Caffeine has a biphasic effect on Ca(2+)-activated K+ current [IK(Ca)]: it induces a transient increase superimposed upon a sustained inhibition. While the transient increase coincides with a rise in [Ca2+]i, the sustained inhibition of IK(Ca) is correlated with a sustained inhibition of the L-type Ca2+ current. The L-type Ca2+ current is also inhibited by other agents that mobilize intracellular Ca2+, including thyrotropin releasing hormone (TRH) and ryanodine, but in a matter distinct from caffeine. Unlike the caffeine effect, the TRH-induced inhibition "washes-out" under whole-cell patch-clamp conditions and is eliminated by intracellular Ca2+ chelators. Likewise, the ryanodine-induced inhibition desensitizes while the caffeine-induced inhibition does not. Simultaneous [Ca2+]i and Ca2+ current measurements show that caffeine can inhibit Ca2+ current without changing [Ca2+]i. Single-channel recordings show that caffeine reduces mean open time without affecting single-channel conductance of L-type channels. Hence the effects of caffeine on ion channels in GH3 cells are attributable both to mobilization of intracellular Ca2+ and to a direct effect on the gating of L-type Ca2+ channels.

Animals↗
PubMed1994

Potassium channel inactivation peptide blocks cyclic nucleotide-gated channels by binding to the conserved pore domain.

Cyclic nucleotide-gated (CNG) channels in photoreceptors and olfactory neurons are activated by intracellular ligands (cAMP and cGMP) rather than voltage. Surprisingly, these channels share amino acid sequence homology with voltage-gated channels. Here we show that the distinct gating mechanisms exhibited by CNG and voltage-gated channels share features that reflect this structural homology. Thus, a 20 amino acid peptide ("ball peptide") derived from the Shaker-type K+ channel and responsible for its rapid inactivation also blocks CNG channels. Moreover, the peptide selectively blocks open CNG channels and prevents channel closure, showing that CNG channel activation, like activation of voltage-dependent K+ channels, involves the opening of a gate located on the intracellular side of the peptide-binding site. Amino acid substitutions in the peptide cause similar changes in blocking affinity of CNG and K+ channels, suggesting a conserved binding site. Using a chimeric retinal/olfactory channel, we show that the difference in the peptide affinity of the two CNG channels is due to a difference in the amino acid sequence of the conserved pore-forming region, demonstrating that this domain forms part of the peptide receptor.

Animals↗
PubMed1994

Metastatic melanoma cells interact with the reticular fibres of the lymph node.

Murine B16 melanoma sublines showing enhanced metastasis to lymph nodes were selected in vivo. Successive selections of tumours metastasizing from the footpad to para-aortic nodes yielded variant tumour cell lines, including an amelanotic line, with moderately increased potential for lymph node metastasis. The phenotype of the variant cells was distinct from that of the parental cells. The lymph node-selected cells had extensive dendritic-like pseudopodial projections and were more motile than the parental cells. In addition, the variant cells were more efficient than the parental cells in attaching to and spreading on preparations of lymph node extracellular matrix. This matrix is composed of an array of reticular fibres containing a core of collagen type III decorated with a basement membrane-like material rich in laminin and type IV collagen. In adhesion assays, the melanoma cells attached best to laminin, collagen, and fibronectin, and poorly to the interstitial matrix proteins collagen types I and III. This pattern of ligand preference was confirmed in adhesion assays to cryostat tissue sections of amnion, in which the tumour cells attached to the basement membrane aspect but not the interstitial stromal matrix. Experiments using specific antibodies established that cell attachment to lymph node reticular fibres was mediated by the beta 1 class of integrin receptor complexes. These results indicate that highly motile variant B16 sublines can be selected for distant lymphatic dissemination, and that interaction between invasive tumour cells and nodal reticular fibres may facilitate this metastatic process.

Animals↗
PubMed1994

Confocal microscopic analysis of integrin expression on the microvasculature and its sprouts in the neonatal foreskin.

Members of the integrin family of adhesion receptors are essential participants in blood vessel growth and remodeling. It is not known which integrins are involved in the initial stages of angiogenesis in vivo. In this study we determined the location of integrins on the blood vessels of a growing tissue, the neonatal foreskin, in which neovascularization is likely to occur. We used the confocal microscope to visually reconstruct vessels from the papillary dermis of the foreskin and to identify potential sprouts as narrow, tapering extensions from these vessels. Blood vessels were initially identified by their positive reaction with antibodies to von Willebrand factor or human platelet endothelial cell adhesion molecule and their negative response to anti-neurofilament antibodies. Later, vessels were identified by their shape and location. We screened vessels with anti bodies to integrin subunits alpha 1, alpha 2, alpha 3, alpha 5, alpha 6, alpha v, beta 1, beta 3 and beta 4. We found that integrin subunits alpha 6 and beta 4 were consistently found along the whole length of capillary loops and extended to the distal ends of presumed sprouts. The alpha 2 and alpha v integrin concentrations, which are normally low in the microvasculature, were increased on the sprouts. alpha 5 was either absent from vessels entirely or more concentrated on the body than on the sprout. alpha 1 was more commonly present on nerves than blood vessels. These studies suggest an important role for the alpha 6 beta 4 integrin in the initial stages of endothelial outmigration during new vessel growth.

Blood Vessels↗
PubMed1994

Ductus arteriosus smooth muscle cell migration on collagen: dependence on laminin and its receptors.

During permanent closure of the ductus arteriosus, smooth muscle cells migrate through the extracellular matrix (ECM) to form intimal mounds that occlude the vessel's lumen. Smooth muscle cells (SMC) migrate over surfaces coated with collagen in vitro. During the migration SMC also synthesize fibronectin (FN) and laminin (LN). Antibodies against FN and LN inhibit migration on collagen by 30% and 67%, respectively. Because of the apparent importance of LN in migration, we examined how SMC interact with LN and LN fragments (P1, E8, P1', E1', E3, E4, and G). Ductus SMC adhere to high concentrations of LN and two fragments of the molecule: P1 and E8. They use a unique set of integrin receptors to bind to LN (alpha 1 beta 1, alpha 6 beta 1 and alpha v beta 3), to P1 (alpha 1 beta 1, alpha v beta 3), and to E8 (alpha 6 beta 1, alpha v beta 3). The alpha v beta 3 integrin binds to the P1 fragment of LN in an RGD peptide-dependent manner, and to the E8 fragment in an RGD-independent manner; the RGD site on the P1 fragment probably is not available to the cell in intact LN. Antibodies against beta 1 integrins completely inhibit SMC adhesion to LN; antibodies against the alpha v beta 3 integrin do not block SMC adhesion to LN, but do prevent cell spreading. LN is also capable of interfering with SMC adhesion to other ECM components. The antiadhesive effect of LN is located in the E1' domain. Both exogenous and endogenous LN increase SMC motility on collagen I. The locomotion-promoting activity of LN resides in the E1' antiadhesive domain, and not in its adhesive (P1, E8) domains. LN causes a decrease in the number of focal contacts on collagen I. This might enable SMC to alter their mobility as they move through the extracellular matrix to occlude the ductus arteriosus lumen.

Amino Acid Sequence↗
PubMed1993

Alternative extracellular and cytoplasmic domains of the integrin alpha 7 subunit are differentially expressed during development.

Examination of cDNAs for the laminin-binding alpha 7 integrin subunit identified two different sequences (designated X1 and X2) coding for the variable region between the III and IV homology repeat domains near the putative ligand-binding site. Sequencing of a mouse alpha 7 genomic clone established that the X1 and X2 regions are derived by mutually exclusive alternative mRNA splicing. Reverse transcriptase-polymerase chain reaction analysis of alpha 7 mRNA indicated that the X1 and X2 isoforms were present in equal amounts in mouse skeletal myoblasts and adult heart. However, in adult skeletal muscle, the X2 variant was exclusively expressed. Amino acid sequence homologies in the III/IV segment suggest that alpha 3 and alpha 6 are also alternatively spliced at this site. We identified alternatively spliced exons in a human alpha 6 genomic clone that encode X1- and X2-like segments. Analysis of the alpha 7 cytoplasmic domain indicated that this region was also alternatively spliced and like alpha 3 and alpha 6 could exist as the A or B form. In mouse skeletal and cardiac muscle the B form of alpha 7 was strongly expressed. However, we identified alpha 7A in neonate and adult skeletal muscle but not in cardiac tissue. High levels of alpha 7A were detected in differentiating myotubes, but in proliferating myoblasts only the alpha 7B isoform was present. These results indicate that alternative splicing of alpha 7 mRNA is differentially regulated during development and generates variant integrin chains with structurally and presumably functionally unique ligand-binding and cytoplasmic domains.

Alternative Splicing↗
PubMed1993

An exact general analysis of ligand binding displacement and saturation curves.

Quantitative analysis of a ligand-protein interaction relates binding to the free concentration of ligand molecules in solution. A theoretical analysis is presented herein, by which intermolecular interactions can be described as a function of the added concentrations of ligand molecules. Following this analysis, ligand binding displacement and saturation curves can be converted directly into a linear form, even when nonradioactively labeled ligands are used to detect the ligand-protein interaction. From the linearities obtained, relevant binding parameters, including the binding dissociation constant, can be calculated. On the basis of this analysis, binding parameters have been characterized for the interaction between biotin-protein A and immunoglobulins, using ELISA-type detection, and for the interaction of a fluorescently labeled fatty acid with a specific fatty acid binding protein.

Animals↗
PubMed1993

Epidermal growth factor (EGF) promotes human keratinocyte locomotion on collagen by increasing the alpha 2 integrin subunit.

The migration of human keratinocytes across the would bed is an early and critical event in the reepithelialization of cutaneous wounds. Epidermal growth factor (EGF) has been shown to accelerate the healing of fresh, split-thickness cutaneous wounds when applied topically. The mechanism(s) by which this accelerated healing occurs remains unknown. Using an assay that directly evaluates human keratinocyte locomotion without confounding the possibility of cell proliferation, we examined the influence of EGF on human keratinocyte motility. Both recombinant epidermal growth factor (rEGF) and transforming growth factor-alpha (TGF-alpha) promoted human keratinocyte locomotion when the cells were apposed to connective tissue matrices of collagen or fibronectin, important components of the wound bed. Other growth factors studied did not enhance keratinocyte migration. Blocking the EGF/TGF-alpha receptor on the cell surface of keratinocytes with specific antibody inhibited the stimulation of keratinocyte locomotion by rEGF and TGF-alpha. Flow cytometry analysis of keratinocytes migrating on type I collagen in the presence of rEGF or TGF-alpha revealed increased expression of the alpha 2 integrin subunit on the keratinocyte surface. The alpha 2 beta 1 integrin mediates keratinocyte migration on collagens type I and IV, and inhibition of migration via antibody blockade of the alpha 2 beta 1 integrin can be partially overcome by increasing the concentration of rEGF present in the medium. Our study demonstrates that the growth-independent stimulation of keratinocyte locomotion via regulation of integrin expression may be one mechanism by which EGF accelerates the reepithelialization of human cutaneous wounds.

Basement Membrane↗
PubMed1993

Expression of integrins and basement membrane components by wound keratinocytes.

Extracellular matrix proteins and their cellular receptors, integrins, play a fundamental role in keratinocyte adhesion and migration. During wound healing, keratinocytes detach, migrate until the two epithelial sheets confront, and then regenerate the basement membrane. We examined the expression of different integrins and their putative ligands in keratinocytes during human mucosal wound healing. Migrating keratinocytes continuously expressed kalinin but not the other typical components of the basement membrane zone: type IV collagen, laminin, and type VII collagen. When the epithelial sheets confronted each other, these missing basement membrane components started to appear gradually through the entire wound area. The expression of integrin beta 1 subunit was increased in keratinocytes during migration. The beta 1-associated alpha 2 and alpha 3 subunits were expressed constantly by wound keratinocytes whereas the alpha 5 subunit was present only in keratinocytes during reepithelialization. Furthermore, migrating cells started to express alpha v-integrins which were not present in the nonaffected epithelium. All keratinocytes also expressed the alpha 6 beta 4 integrin during migration. In the migrating cells, the distribution of integrins was altered. In normal mucosa, beta 1-integrins were located mainly on the lateral plasma membrane and alpha 6 beta 4 at the basal surface of basal keratinocytes in the nonaffected tissue. In wounds, integrins were found in filopodia of migrating keratinocytes, and also surrounding cells in several cell layers of the migrating sheet. The results indicate that migrating keratinocytes, in deep human wounds enlarge their integrin repertoire. The changes in integrin expression take place concomitantly with changes in the basement membrane composition, suggesting a close interplay of these two groups of molecules during wound healing.

Antibodies, Monoclonal↗
PubMed1992

Mechanism of human keratinocyte migration on fibronectin: unique roles of RGD site and integrins.

The migration of human keratinocytes over the wound bed plays an important role in the re-epithelialization of cutaneous wounds. Fibronectin, a large glycoprotein matrix component that is abundant within cutaneous wound beds, promotes keratinocyte migration. However, the mechanisms by which keratinocytes migrate over fibronectin are unknown. In this study, we sought to identify specific sites within the fibronectin molecule that induce keratinocyte locomotion and to characterize the cell surface receptors involved. The data show that the domain within the fibronectin molecule that induces human keratinocyte migration is the 120 kD cell-binding domain close to the carboxyl terminus. The 40 kD heparin-binding domain near the carboxyl terminus and the 45 kD gelatin-binding domain near the amino terminus did not promote keratinocyte migration. In addition, keratinocyte migration on both fibronectin and the 120 kD cell-binding domain was completely inhibited by the presence of GRGDSP peptide, suggesting that keratinocyte migration on fibronectin is mediated by recognizing the RGD sequence located within the cell-binding domain of fibronectin. Furthermore, keratinocytes were able to migrate directly on immobilized RGD substratum. Cell migration on fibronectin is mediated by the alpha 5 beta 1 integrin since antibodies blocking the alpha 5 and the beta 1 subunits completely inhibited keratinocyte migration on fibronectin. In addition, we demonstrate that human keratinocytes express alpha 5 beta 1 integrin in culture by flow cytometry.

Binding Sites↗
PubMed1992

Basic FGF and TGF-beta differentially modulate integrin expression of human microvascular endothelial cells.

Basic fibroblast growth factor (bFGF) and transforming growth factor-beta (TGF-beta) are known to alter the migratory and proliferative capacity of endothelial cells in vitro and to stimulate angiogenesis in vivo. One mechanism by which these cytokines induce their effects may be through the regulation of integrin adhesion receptor expression and activity. We examined the ability of these growth factors to modulate the expression of specific integrins in human microvascular endothelial cells (MEC). Immunoprecipitation of metabolically labeled MEC showed that bFGF upregulated the biosynthesis of alpha 2, alpha 5, beta 1, and beta 3. bFGF induced an increase in the levels of mRNA for alpha 2 and beta 1. TGF-beta increased synthesis of alpha 2, alpha 5, and beta 1. These results suggest that bFGF and TGF-beta selectively alter integrin profiles and influence interactions of MEC with the extracellular matrix during neovascularization. In particular, the upregulation of the collagen/laminin receptor, alpha 2 beta 1, by bFGF may provide activated endothelial cells with an enhanced capacity to migrate through both their underlying basement membrane and the interstitial matrix.

Cells, Cultured↗
PubMed1992

Beta 1 and beta 3 integrins have different roles in the adhesion and migration of vascular smooth muscle cells on extracellular matrix.

Extracellular matrix receptors on ductus arteriosus smooth muscle cells (SMC) must enable the cells to migrate through both interstitial and basement membrane matrices to form intimal mounds during postnatal ductus closure. We examined the role of beta 1 and beta 3 integrin receptors on SMC adhesion and migration. Using a new assay to measure cell migration, we found that lamb ductus arteriosus SMC attach to and migrate over surfaces coated with fibronectin (FN), laminin (LN), vitronectin (VN), and collagens I (I) and IV (IV). Blocking antibodies, specific to different integrin complexes, showed that SMC adhesion to FN, LN, I, and IV depended exclusively on functioning beta 1 integrins with little, if any, contribution by the alpha V beta 3 integrin; on the other hand, cell migration over these substrates depended to a large extent on the alpha V beta 3 receptor. Immunofluorescent staining demonstrated that during the early phase of SMC migration, the beta 1 integrins organized rapidly into focal plaques that, with time, gradually covered the cell's basal surface; on the other hand, the beta 3 receptor remained concentrated at all times at the cell's margins. Ligand affinity chromatography and immunoprecipitation techniques identified a unique series of beta 1 integrins binding to each matrix component: FN (alpha 5 beta 1, alpha 3 beta 1, alpha V beta 1), LN (alpha 1 beta 1, alpha 7 beta 1), VN (alpha V beta 1), I (alpha 1 beta 1, alpha 2 beta 1), and IV (alpha 1 beta 1). In contrast, the beta 3 integrin, alpha V beta 3, bound to all the substrates tested: FN, LN, VN, I, and IV. The results indicate that beta 1 and beta 3 integrins may play different roles in attachment and migration as SMC move through the vascular extracellular matrix to produce obliteration of the ductus arteriosus lumen.

Amino Acid Sequence↗