Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Integrin beta3”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

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

At least 937 records · Page 52Linked to original sources
PubMed1999

Involvement of beta2-microglobulin and integrin alphavbeta3 molecules in the coxsackievirus A9 infectious cycle.

It is becoming apparent that many viruses employ more than one cell surface molecule for their attachment and cell entry. In this study, we have tested the role of integrin alpha(v)beta3 and MHC class I molecules in the coxsackievirus A9 (CAV-9) infectious cycle. Binding experiments utilizing CHO cells transfected and expressing human integrin alpha(v)beta3, revealed that CAV-9 particles were able to bind to cells, but did not initiate a productive cell infection. Antibodies specific for integrin alpha(v)beta3 molecules significantly reduced CAV-9 infection in susceptible cell lines. Moreover, MAbs specific for beta2-microglobulin (beta2-m) and MHC class I molecules completely inhibited CAV-9 infection. To assess the effect of these antibodies on virus binding, we analysed CAV-9 binding by flow cytometry in the presence of alpha2-m- or integrin alpha(v)beta3-specific antibodies. The results showed a reduction in CAV-9 binding in the presence of integrin alpha(v)beta3-specific antibodies while there was no reduction in the presence of beta2-m-specific MAb. Taken together, these data suggest that integrin alphavbeta3 is required for CAV-9 attachment but is not sufficient for cell entry, while beta2-m, although not directly involved in CAV-9 binding, plays a post-attachment role in the CAV-9 infectious process, possibly being involved in virus entry.

Animals↗
PubMed2004

Alpha5beta1, alphaVbeta3 and the platelet-associated integrin alphaIIbbeta3 coordinately regulate adhesion and migration of differentiating mouse trophoblast cells.

During blastocyst implantation, interaction between integrins on the apical surface of the trophoblast and extracellular matrix (ECM) in the endometrium anchors the embryo to the uterine wall. Strong adhesion of the blastocyst to fibronectin (FN) requires integrin signaling initiated by exogenous fibronectin. However, it is not known how integrin signaling enhances blastocyst adhesion. We present new evidence that the integrin, alphaIIbbeta3, plays a key role in trophoblast adhesion to fibronectin during mouse peri-implantation development. Trafficking of alphaIIb to the apical surface of the trophoblast increased dramatically after blastocysts were exposed to fibronectin, whereas other fibronectin-binding integrins, alpha5beta1 and alphaVbeta3, were resident at the apical surface before ligand exposure. Functional comparisons among the three integrins revealed that ligation of alpha5beta1 most efficiently strengthened blastocyst fibronectin-binding activity, while subsequent trophoblast cell migration was dependent primarily on the beta3-class integrins. In vivo, alphaIIb was highly expressed by invasive trophoblast cells in the ectoplacental cone and trophoblast giant cells of the parietal yolk sac. These data demonstrate that trafficking of alphaIIb regulates adhesion between trophoblast cells and fibronectin as invasion of the endometrium commences.

Animals↗
PubMed2001

The cribriform features of adenoid cystic carcinoma and polymorphous low-grade adenocarcinoma: cytokeratin and integrin expression.

Cribriform areas are common features of both adenoid cystic carcinoma and polymorphous low-grade adenocarcinoma. Both are malignant salivary gland tumors that share similar histologic patterns, but with marked distinct clinical behavior. This study was undertaken to improve the accuracy of the histopathology diagnostic process, using an immunohistochemical panel to differentiate adenoid cystic carcinoma from polymorphous low-grade adenocarcinoma, with special concern to the common cribriform areas shared by these tumors. Three-microm serial sections of these tumors were submitted to the streptavidin-biotin peroxidase immunotechnique against the monoclonal antibodies anticytokeratins 7, 8, 14 and 19, and anti-integrins beta1, beta3, and beta4. In the neoplastic lobules of adenoid cystic carcinoma cribriform type, the spaces were mainly surrounded by cells negative for the cytokeratins and integrins studied. In the solid type of adenoid cystic carcinoma, the microcystic areas were caused by spaces lined by neoplastic luminal cells positive for cytokeratins and presenting integrins concentrated in the apical pole of these cells. The cribriform areas of polymorphous low-grade adenocarcinoma were composed of cords of luminal cells, positive for cytokeratins and showing integrins disposed in a bipolar pattern. We concluded that cribriform areas of adenoid cystic carcinoma and polymorphous low-grade adenocarcinoma are histologically similar, although not identical. Indeed, their cellular composition is distinct and can be distinguishable from one another by the proteins of the cytoskeleton, by the integrins, or both.

Adenocarcinoma↗
PubMed1999

A chimeric cell adhesion molecule mediates homing of lymphocytes to vascularized tumors.

To facilitate tumor colonization by adoptively transferred cells of the immune system, we created a chimeric cell adhesion molecule that mediates tumor-specific homing by binding to the integrin alpha(v)beta3 on angiogenic endothelial cells. A high-affinity cell adhesion molecule for integrin alpha(v)beta3 was generated by fusing the disintegrin kistrin to the transmembrane adhesion molecule CD31/PECAM-1. This chimeric cell adhesion molecule, termed KISS31, mediates adhesion of lymphoid cells to soluble recombinant integrin alpha(v)beta3 and to endotheliomal monolayers in vitro. KISS31-expressing lymphoid cells accumulate in angiogenic tumors in two in vivo models, in B16/129 melanoma xenografts on the chick chorioallantois and in s.c. growing Lewis lung carcinoma in mice. Our data indicate that expression of KISS31 on lymphoid cells confers tumor-specific homing. This is, to our knowledge, the first example of an experimental mechanism that targets living cells to tumors by redirecting their homing pattern.

Amino Acid Sequence↗
PubMed2005

Gal3ST-2 involved in tumor metastasis process by regulation of adhesion ability to selectins and expression of integrins.

In this study, significantly higher expression of Gal3ST-2 (Gal: 3-O-sulfotransferase-2) and 3'-sulfated glycoconjugates were observed in highly metastastic cancer cells and in larynx cancer tissues with lymph node metastasis than those in lowly metastatic cancer cells and larynx cancer tissues without metastasis (P<0.01, n=42). These results indicated that there was a marked correlation between the expression of Gal3ST-2 and tumor metastasis potential. After RNAi transfection, a striking morphological change of SMMC7721 hepatoma cells from polygon to shuttle shape and significant decrease in adhesion to sL-selectin and HUVEC were observed. Interestingly, the expression of integrin subunit alphaV was markedly downregulated and 3'-sulfated subunit alphaV almost disappeared in the transfectants, but integrin subunit beta3 almost had no change. These results suggested that Gal3ST-2 was involved in tumor metastasis process by regulation of adhesion ability to selectins and expression of integrins.

Blotting, Western↗
PubMed2003

Integrins expressed with bladder extracellular matrix after stretch injury in vivo mediate bladder smooth muscle cell growth in vitro.

PURPOSE: It is unknown how bladder smooth muscle cells sense extrinsic mechanical stimuli. The integrins are a large versatile family of transmembrane mechanoreceptors that transduce extracellular matrix (ECM) alterations into the cell, thereby, regulating proliferation, differentiation and ECM synthesis. To our knowledge we provide the first evidence that the integrins may be involved in responses to whole bladder distention and bladder smooth muscle cell stretch. MATERIALS AND METHODS: Bladders from 100 to 120 gm. rats were stretched to 40 cm. H2O for 5 minutes. Five to 96 hours after distention whole bladder mRNAs were isolated for analysis of temporal expression of collagen and integrin genes. Separately quiescent primary culture bladder smooth muscle cells from 1-day-old Sprague-Dawley rats were stretched cyclically for 4 hours. Relative expression of select integrin subunit mRNAs was assessed by semiquantitative reverse transcriptase-polymerase chain reaction. Integrin blockade with asparagine-glycine-arginine peptides was used to determine the role of integrins in stretch induced proliferation and the cell cycle in bladder smooth muscle cells. RESULTS: Within 24 hours bladder distention stimulated collagen expression 2-fold (type I) and 5-fold (type III). Collagen levels beyond 24 hours were 8-fold (type I) and 2-fold (type III) greater than in controls, revealing an inverse temporal type I-to-III ratio beyond 24 hours. Coordinate alterations were observed in integrin and collagen expression. In vitro bladder smooth muscle cell integrin beta1, beta3 and alphav subunit expression was increased by mechanical stretch 2.5, 3.8 and 5-fold, respectively, while alpha1 expression decreased. Asparagine-glycine-arginine peptide inhibition of integrin function significantly inhibited stretch induced bladder smooth muscle cell proliferation and exit from the G2/M phase of the cell cycle. CONCLUSIONS: To our knowledge these results demonstrate for the first time that that bladder distention initiates dynamic alterations in ECM expression. The ability of integrin blockade to suppress stretch induced bladder smooth muscle cell proliferation and the coordinate changes in bladder ECM and integrin expression suggest that integrins mediate key responses to mechanical stimuli in the bladder. Furthermore, cell cycle analysis of resting and stretched bladder smooth muscle cells revealed novel avenues for the examination of integrin and stretch regulation of bladder smooth muscle cell growth.

Animals↗
PubMed2003

Involvement of the beta3 E749ATSTFTN756 region in stabilizing integrin alphaIIbbeta3-ligand interaction.

Platelet integrin alphaIIbbeta3 must be activated via intracellular mechanisms before it binds soluble ligands, and it is thought to be activated at its extracellular site by surface-bound ligands. Integrin activation is associated with rearrangement of the cytoskeleton and phosphorylation of proteins that become localized in focal contacts. In these processes, the cytoplasmic tail of the beta-subunit plays a central role. We introduced peptides homologous to the E749ATSTFTN756 domain (E-N peptide) and the T755NITYRGT762 domain (T-T peptide) of beta3 in streptolysin O-permeabilized platelets and analyzed the initial interaction with soluble fibronectin, fibrinogen and PAC-1 after stimulation with thrombin. E-N peptide left the initial binding of fibronectin intact but interfered with stable receptor occupancy. E-N peptide also inhibited fibrinogen binding, thereby reducing the formation of large aggregates. Strikingly, E-N peptide did not disturb the binding of PAC-1, which is known to reflect activation of the integrin. E-N peptide also inhibited tyrosine phosphorylation of focal adhesion kinase, a response known to be dependent on alphaIIbbeta3. T-T peptide did not affect these processes. In a model for outside-in integrin activation, E-N peptide disrupted the binding of CHO cells expressing alphaIIbbeta3 to surface-bound ligand. Again, T-T peptide had no effect. We conclude that the E749ATSTFTN756 region of the beta3-tail stabilizes the binding of soluble and surface-bound ligand to integrin alphaIIbbeta3 via a mechanism that involves the phosphorylation of FAK.

Animals↗
PubMed2003

Osteopetrosis and Glanzmann's thrombasthenia in a child.

Autosomal recessive osteopetrosis is a rare, fatal disease characterized by accumulation of excessive bone mass due to defective bone resorption. The pathogenesis of osteopetrosis is controversial. Osteoblast-osteoclast interaction defects, incorrect differentiation of osteoclasts, abnormal contact between osteoclast and extracellular matrix, and abolished signaling are included in this process. Recently, mutations in the gene of the vacuolar proton pump have been described in some cases of recessive osteopetrosis. Glanzmann's thrombasthenia (GT) is a rare hereditary qualitative platelet disorder characterized by a lifelong bleeding tendency due to quantitative and qualitative abnormalities of the platelet integrin alpha(IIb) beta3. Several mutations on either integrin alpha(IIb) [glycoprotein (GP) IIb] or integrin beta(3) (GP IIIa) were reported in GT. We report on a patient with autosomal recessive osteopetrosis concurrently diagnosed with variant type Glanzmann's thrombasthenia. To our knowledge, our patient was the first case reported in the literature in which osteopetrosis and Glanzmann's thrombasthenia were diagnosed together.

Genes, Recessive↗
PubMed2001

Antagonism of the osteoclast vitronectin receptor with an orally active nonpeptide inhibitor prevents cancellous bone loss in the ovariectomized rat.

An orally active, nonpeptide Arg-Gly-Asp (RGD) mimetic alpha(v)beta3 antagonist, (S)-3-Oxo-8-[2-[6-(methylamino)-pyridin-2-yl]-1-ethoxy]-2-(2,2,2-trifluoroethyl)-2,3,4,5-tetrahydro-1H-2-benzazepine-4-acetic acid (compound 1), has been generated, which prevented net bone loss and inhibited cancellous bone turnover in vivo. The compound binds alpha(v)beta3 and the closely related integrin alpha(v)beta5 with low nanomolar affinity but binds only weakly to the related integrins alpha(IIb)beta3, and alpha5beta1. Compound 1 inhibited alpha(v)beta3-mediated cell adhesion with an IC50 = 3 nM. More importantly, the compound inhibited human osteoclast-mediated bone resorption in vitro with an IC50 = 11 nM. In vivo, compound 1 inhibited bone resorption in a dose-dependent fashion, in the acute thyroparathyroidectomized (TPTX) rat model of bone resorption with a circulating EC50 approximately 20 microM. When dosed orally at 30 mg/kg twice a day (b.i.d.) in the chronic ovariectomy (OVX)-induced rat model of osteopenia, compound 1 also prevented bone loss. At doses ranging from 3 to 30 mg/kg b.i.d., compound 1 partially prevented the OVX-induced increase in urinary deoxypyridinoline. In addition, the compound prevented the OVX-induced reduction in cancellous bone volume (BV), trabecular number (Tb.N), and trabecular thickness (Tb.Th), as assessed by quantitative microcomputerized tomography (microCT) and static histomorphometry. Furthermore, both the 10-mg/kg and 30-mg/kg doses of compound prevented the OVX-induced increase in bone turnover, as measured by percent osteoid perimeter (%O.Pm). Together, these data indicate that the alpha(v)beta3 antagonist compound 1 inhibits OVX-induced bone loss. Mechanistically, compound 1 prevents bone loss in vivo by inhibiting osteoclast-mediated bone resorption, ultimately preventing cancellous bone turnover.

Animals↗
PubMed2001

Signaling mechanisms underlying strain-dependent brain natriuretic peptide gene transcription.

Activation of brain natriuretic peptide (BNP) gene promoter activity represents one of the earliest and most reliable markers of ventricular cardiac myocyte hypertrophy. We recently demonstrated that mechanical strain increases immunoreactive BNP secretion, steady-state BNP mRNA levels and BNP gene transcriptional activity in neonatal rat myocyte cultures. We have also shown that strain-dependent BNP gene transcription is critically dependent on the functional integrity of a number of integrins (specfically beta1, beta3, and alpha(v)beta5 integrins) present on the surface of cardiac myocytes. When used alone, each of these antibodies resulted in a significant reduction in strain-dependent activation of a transfected hBNP-luciferase reporter and inhibition of a number of signaling pathways that have been linked to stimulation of this reporter (e.g., extracellular signal regulated kinase and c-Jun amino terminal kinase). The present study shows that combinations of these antibodies resulted in further reductions in hBNP gene promoter activity and inhibition of the relevant signaling cascades. These studies provide further support for the importance of integrin-matrix interactions in promoting strain-dependent changes in cardiac myocyte gene transcription.

Animals↗
PubMed1998

Identification of the ligand binding site for the integrin alpha9 beta1 in the third fibronectin type III repeat of tenascin-C.

The integrin alpha9 subunit forms a single heterodimer, alpha9 beta1 that mediates cell adhesion to a site within the third fibronectin type III repeat of tenascin-C (TNfn3). In contrast to at least 3 other integrins that bind to this region of tenascin-C, alpha9 beta1 does not recognize the common integrin recognition motif, Arg-Gly-Asp (RGD). In this report, we have used substitution mutagenesis to identify a unique ligand recognition sequence in TNfn3. We introduced mutations substituting alanine for each of the acidic residues in or adjacent to each of the exposed loops predicted from the solved crystal structure. Most of these mutations had little or no effect on adhesion of alpha9-transfected SW480 colon carcinoma cells, but mutations of either of two acidic residues in the B-C loop region markedly reduced attachment of these cells. In contrast, cells expressing the integrin alphav beta3, previously reported to bind to the RGD sequence in the adjacent F-G loop, attached to all mutant fragments except one in which the RGD site was mutated to RAA. The peptide, AEIDGIEL, based on the sequence of human tenascin-C in this region blocked the binding of alpha9-transfected cells, but not beta3-transfected cells to wild type TNfn3. This sequence contains a tripeptide, IDG, homologous to the sequences LDV, IDA, and LDA in fibronectin and IDS in VCAM-1 recognized by the closely related integrin alpha4 beta1. These findings support the idea that this tripeptide motif serves as a ligand binding site for the alpha4/alpha9 subfamily of integrins.

Amino Acid Sequence↗
PubMed2002

Two different beta3 cysteine substitutions alter alphaIIb beta3 maturation and result in Glanzmann thrombasthenia.

We report the defects responsible for Glanzmann thrombasthenia in two patients showing traces of abnormally migrating platelet beta3 in immunoblotting. Using PCR-SSCP and direct sequencing, we identified a novel homozygous mutation in exon 10 of the beta3 gene of patient 1 which gave a C457 to Y amino acid substitution. A C542 to R substitution in beta3 of patient 2 was previously reported by us. These cysteines are present in EGF-domains 1 and 3 respectively of beta3. We therefore constructed mutants carrying substitutions on cysteine residues in each of the first three EGF domains of beta3, C457, C495 and C542 respectively. Transient expression of these mutants in COS-7 cells, including the C542 and C547 double mutant, proved that disulfide disruption directly affects cell surface expression of the integrin. We then showed by metabolic (35S) labeling and Endo-H glycosidase treatment that these substitutions strongly affected complex maturation within the cell.

Amino Acid Substitution↗
PubMed1996

Ligand binding to integrin alphaIIbbeta3 is dependent on a MIDAS-like domain in the beta3 subunit.

Substitution of beta3 residue Asp119, Ser121, or Ser123 results in a loss of the ligand binding function of integrin alphaIIbbeta3. Homologous residues in other integrin beta subunits are similarly critical for ligand binding function. This DXSXS motif is also present in the I domain of certain integrin alpha subunits, where it constitutes a portion of the unique metal ion-dependent adhesion site (MIDAS). In this report, we have utilized the crystal structure of the recombinant alphaM I domain to produce a three-dimensional model of the homologous region in the integrin beta3 subunit. We performed mutagenesis of candidate amino acid residues predicted from this model to be involved in cation coordination and ligand binding. We report the identification of Asp217 and Glu220 as residues essential for the ligand binding function of alphaIIbbeta3. Alanine substitution of these residues did not affect receptor expression but abolished the binding of activation-dependent (PAC1) and -independent (OPG2) ligand mimetic antibodies. In our proposed model, beta3 Asp217 is analogous to a metal-coordinating residue in the alphaM MIDAS domain, while Glu220 does not correspond to a functional MIDAS domain residue. Substitution of the highly conserved beta3 residue Thr197 corresponding to a critical MIDAS metal-coordinating Thr residue did not affect ligand binding function, suggesting that this region of beta3 adopts a structure that is very similar to but not identical to that of the MIDAS domain. These data support a functional linkage between these two sequences and further define a common feature of ligand binding to integrins.

Amino Acid Sequence↗
PubMed1998

A type II phosphoinositide 3-kinase is stimulated via activated integrin in platelets. A source of phosphatidylinositol 3-phosphate.

We have observed that aggregation of human platelets, caused by activation of integrin alphaIIb beta3 and its consequent binding of fibrinogen, stimulates a novel pathway for synthesis of phosphatidylinositol 3,4bisphosphate, thereby activating protein kinase B/Akt. Such synthesis depends upon both the generation of phosphatidylinositol 3-phosphate (PtdIns3P), which is sensitive to wortmannin (IC50 7 nM) and calpain inhibitors, and the phosphorylation of PtdIns3P by PtdIns3P 4-kinase. We now report that a recently characterized C2 domain-containing phosphoinositide 3-kinase isoform (HsC2-PI3K) is present in platelets and a leukemic cell line (CHRF-288) derived from megakaryoblasts, and is likely to be responsible for the stimulated synthesis of PtdIns3P observed in platelets. HsC2-PI3K, identifiable by Western blotting and immunoprecipitatable activity, is sensitive to wortmannin (IC50 6-10 nM), requires Mg2+, and shows strong preference for PtdIns over PtdIns4P or phosphatidylinositol 4,5-bisphosphate as substrate. HsC2-PI3K is activated severalfold when platelets aggregate in an alphaIIb beta3-dependent manner or when platelet or CHRF-288 lysates are incubated with Ca2+. Activation is prevented by calpain inhibitors. CHRF-288, which cannot undergo activation of alphaIIb beta3 and thereby aggregate in response to platelet agonists, do not generate PtdIns3P or activate HsC2-PI3K under conditions that stimulate other phosphoinositide 3-kinases. HsC2-PI3K may thus be an important effector for integrin-dependent signaling.

Androstadienes↗
PubMed2001

Recognition of multiple antibody epitopes throughout Borrelia burgdorferi p66, a candidate adhesin, in patients with early or late manifestations of Lyme disease.

Antibody responses to p66, a candidate integrin ligand of Borrelia burgdorferi, were studied in 79 patients with early or late manifestations of Lyme disease. The central portion of p66 was previously shown to contain all of the information required for specific recognition of beta3-chain integrins, but work by others had suggested that the C-terminal portion of the protein contains a single surface-exposed, immunodominant loop. In examining antibody responses to full-length p66 and to three overlapping fragments of the protein, we found that the majority of Lyme disease patients had immunoglobulin M (IgM) and/or IgG responses to p66 and that, particularly early in the disease, epitopes throughout p66 were recognized. Among patients with later manifestations of the illness, antibody responses to the C-terminal portion of the protein were more prominent. These results demonstrate that Lyme disease patient sera recognize epitopes throughout p66.

Antibodies, Bacterial↗
PubMed1998

A plant surface protein sharing structural properties with animal integrins.

Using a polyclonal antibody (P23) generated against the human platelet integrin aIIb beta3 and a FITC-conjugate secondary antibody, fluorescence is observed at the surface of protoplasts isolated from Arabidopsis thaliana and Rubus fruticosus. Arabidopsis thaliana cells grown in suspension culture containing P23 and glycylarginylglycylaspartylserine (GRGDS), a synthetic peptide containing the RGD sequence found in many extracellular matrix adhesive proteins demonstrated aberrant cell wall/plasma membrane interactions and organization. When glycoproteins from these plants, purified on a concanavalin A Sepharose 4B, were subjected to SDS/PAGE and Western blotting, under reduced and non-reduced conditions, immunoblots probed with P23 revealed bands in both species. A shift in electrophoretic mobility is observed to different apparent molecular mass when no reducing agent is present. When purified by immunoaffinity chromatography on anti-aIIb beta3 Sepharose or Sepharose linked to the synthetic peptide D-Arg-Gly-Asp-Trp, the major antigenic components detected migrate at 30 kDa and 60 kDa in the first experiment and 60 kDa in the second one. Only the 60-kDa component is immunodetected with antibodies specific for either the beta3 platelet chain or the aIIb polypeptide, suggesting the presence of two polypeptides co-migrating. To address more precisely the structure of this complex in plants, competition assays were performed. A significant inhibition is observed with CS3 a monoclonal antibody that interacts with the complexed form aIIb beta3 but not the dissociated subunits. Further structural similarities with the animal aIIb beta3 complex is demonstrated with Western blotting detection after plant glycoproteins immunoprecipitation with CS3 in absence or presence of 5 mM EDTA to dissociate the complex. We also present data on the characterization of a polyclonal antibody, named AcAt2, raised against Arabidopsis glycocoproteins purified by affinity chromatography on a D-RGDW column and eluted with the same peptide, that specifically interacts with the animal aIIb beta3 receptor.

Amino Acid Sequence↗
PubMed1999

DNA sequence of the canine platelet beta3 gene from cDNA: comparison of canine and mouse beta3 to segments that encode alloantigenic sites and functional domains of beta3 in human beings.

The platelet glycoprotein complex alphaIIb beta3 is required for platelet-fibrinogen binding and platelet aggregation. This study was designed to characterize the nucleotide sequence of the canine platelet beta3 gene from cDNA. The nucleotide and deduced amino acid sequences of the canine beta3 gene were 92% and 96% homologous, respectively, with the sequences previously established for the beta3 gene of human beings. Within the beta3 gene, the nucleotide sequence of cDNA prepared from canine platelets shared homology of 89% for the cytoplasmic domain, 93% for the transmembrane domain, 92% for the extracellular domain, 94% for the arginine-glycine-aspartic acid (RGD) binding domain, and 97% for the region associated with Ca2+-dependent stabilization of the alphaIIb beta3 fibrinogen-binding pocket. The deduced amino acid sequence of canine beta3 was 100%, 97%, 96%, and 95% homologous with the cytoplasmic, transmembrane, extracellular, and RGD-binding domains, respectively, and was 100% homologous with the region associated with Ca2+-dependent stabilization of the alphaIIb beta3 fibrinogen-binding pocket of beta3 in human beings. The canine platelet cDNA signal peptide segment of the beta3 gene encodes for 22 amino acids, as compared with 26 amino acids previously reported for human beings. The deduced amino acid sequence of canine beta3 corresponds to the high-frequency allelic form for five of the six alloantigenic sites reportedly associated with human platelets: Leu33Leu40Pro407Arg489Arg636. The apparent amino acid residue in position 143 (Pen alloantigen) of canine platelet beta3 is histidine compared with arginine in human beings. Knowledge of the beta3 gene nucleotide sequence of normal dogs will facilitate the understanding of platelet alphaIIb beta3 structure-function relationships.

Amino Acid Sequence↗