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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The developmentally regulated expression of fibronectin (FN) in developing organs and FN's ability to stimulate cell migration and differentiation in vitro suggest a role in organogenesis. We examined the distribution of FN and the alpha 5 subunit of its receptor, the integrin alpha 5 beta 1, in the lungs and hearts of murine embryos at 11, 13, 16, and 18 days of gestation. In the lung, FN staining was present in the mesenchyme and parabronchial cells at day 11, increased at day 13, and decreased after day 16. Increases in FN coincided with the period of branching morphogenesis, and FN was concentrated at areas of airway bifurcation, suggesting a role for FN in cleft formation. The alpha 5 subunit appeared later at 13 days, co-distributing with FN only in well-developed primary bronchioles. At all stages, alpha-smooth muscle actin expression correlated temporally and spatially with that of the alpha 5 subunit. In the heart, staining for FN, the alpha 5 subunit, and alpha-smooth muscle actin were present at day 11 and increased at day 13. FN was present in the outflow tract and developing atria and ventricles, where it was concentrated in the outer layer or visceral pericardium. Interestingly, alpha 5 was detected at the inner layer, the endothelium, lining the outflow tract and atrioventricular cushions where endothelial cells migrate into the cardiac jelly in the process of epithelial-mesenchymal transformation. This suggests a potential role for alpha 5 beta 1 and FN in ventricular septation and valve formation.(ABSTRACT TRUNCATED AT 250 WORDS)
Am J Respir Cell Mol Biol 1992 May
PMID:Expression of fibronectin, the integrin alpha 5, and alpha-smooth muscle actin in heart and lung development. 153 75

The integrins are a family of transmembrane glycoproteins that serve as cell-cell and cell-substratum adhesion molecules and help regulate cellular morphology, differentiation, and proliferation. The integrin repertoire of a cell may therefore influence its behavior under resting conditions or following malignant transformation. For this reason, the distribution of integrins in normal lung tissues was determined using monoclonal antibodies against integrins of the beta 1 (VLA) and beta 3 (cytoadhesin) subfamilies and compared with the distribution in a limited number of lung carcinomas. The integrin subunits that bind to collagen and laminin (alpha 1, alpha 2, alpha 3, and alpha 6) and the alpha subunit, which can pair with beta 1, beta 3, or beta 5 and promote fibronectin, fibrinogen, or vitronectin binding, were the predominant integrins expressed on the major cell types of the lung, i.e., bronchial epithelium, vascular endothelium, and smooth muscle. Strong expression of the alpha 5 beta 1 fibronectin receptor and the beta 3 subunit was restricted to the endothelium of large vessels. Integrin expression by the lung carcinoma cells was somewhat heterogeneous; however, the tumors tended to express fewer integrins than did the normal bronchial epithelium.
Am J Respir Cell Mol Biol 1992 Feb
PMID:Distribution of integrin cell adhesion receptors in normal and malignant lung tissue. 154 Mar 82

Transforming growth factor-beta (TGF-beta) is a secreted polypeptide factor that is thought to play a major role in the regulation of proliferation of many cell types and various differentiation processes. Several related isoforms have been structurally characterized, three of which, TGF-beta 1, -beta 2, and -beta 3, have been detected in mammalian cells and tissues. Each TGF-beta form is a homodimer of a 112-amino-acid polypeptide which is encoded as a larger polypeptide precursor. We have introduced several mutations in the TGF-beta 1 precursor domain, resulting in an inhibition of TGF-beta 1 secretion. Coexpression of these mutants with wild-type TGF-beta 1, -beta 2, and -beta 3 results in a competitive and specific inhibition of the secretion of different TFG-beta forms, indicating that these mutated versions act as dominant negative mutants for TGF-beta secretion. Overexpression of dominant negative mutants can thus be used to abolish endogenous secretion of TGF-beta and structurally related family members, both in vitro and in vivo, and to probe in this way the physiological functions of the members of the TGF-beta superfamily.
Mol Cell Biol 1992 Apr
PMID:Dominant negative mutants of transforming growth factor-beta 1 inhibit the secretion of different transforming growth factor-beta isoforms. 154 20

Transforming growth factor beta (TGF-beta) is the name of a group of closely related polypeptides characterized by a multiplicity of effects, including regulation of extracellular proteolysis and turnover of the extracellular matrix. Its cellular mechanism of action is largely unknown. TGF-beta 1 is a strong and fast inducer of type 1 plasminogen activator inhibitor gene transcription. We have identified a TGF-beta 1-responsive element in the 5'-flanking region of the human type 1 plasminogen activator inhibitor gene and shown that it is functional both in its natural context and when fused to a heterologous nonresponsive promoter. Footprinting and gel retardation experiments showed that two different nuclear factors, present in extracts from both TGF-beta 1-treated and nontreated cells, bind to adjacent sequences contained in the responsive unit. A palindromic sequence binds a trans-acting factor(s) of the CCAAT-binding transcription factor-nuclear factor I family. A partially overlapping dyad symmetry interacts with a second protein that much evidence indicates to be USF. USF is a transactivator belonging to the basic helix-loop-helix family of transcription factors. Mutations which abolish the binding of either CCAAT-binding transcription factor-nuclear factor I or USF result in reduction of transcriptional activation upon exposure to TGF-beta 1, thus showing that both elements of the unit are necessary for the TGF-beta 1 response. We discuss the possible relationship of these findings to the complexity of the TGF-beta action.
Mol Cell Biol 1992 Apr
PMID:Transforming growth factor beta 1-responsive element: closely associated binding sites for USF and CCAAT-binding transcription factor-nuclear factor I in the type 1 plasminogen activator inhibitor gene. 154 30

The B800-820 light-harvesting complex, an integral membrane protein, from Rhodopseudomonas acidophila strain 7750 has been crystallized. The tabular plates have a hexagonal unit cell of a = b = 121.8 A and c = 283.1 A and belong to the space group R32. X-ray diffraction data have been collected to 6 A resolution, using an area detector on a rotating anode source. The B800-820 light-harvesting complex is comprised of four low molecular weight apoproteins (B800-820 alpha 1, B800-820 alpha 2, B800-820 beta 1 and B800-820 beta 2). Polyacrylamide gel electrophoresis shows that the complex exists as an oligomeric assembly, with an apparent molecular weight of 92,000.
J Mol Biol 1992 Mar 20
PMID:Crystallization of the B800-820 light-harvesting complex from Rhodopseudomonas acidophila strain 7750. 156 Apr 69

The integrin receptors are heterodimers whose alpha and beta subunits are encoded by separate, evolutionarily unrelated multigene families. Phylogenetic analysis of DNA sequences from these two gene families showed that they have not always evolved in a parallel fashion. The integrin alpha chains that can form heterodimers with beta 1 do not constitute a monophyletic group, nor do the beta chains which can form heterodimers with alpha V. On the other hand, the vertebrate alpha chains associating with beta 2 are a monophyletic group. In the metal cation-binding region of the alpha chain, an exon exchange took place between human alpha M and alpha X approximately 40-50 Mya, homogenizing this functionally important region in these two alpha chains. When integrin beta chains of different functional classes are compared, nonsynonymous (amino acid altering) nucleotide substitutions that alter amino acid residue charge in the central region of the molecule occur at a rate significantly higher than that expected under random replacement. By contrast, when closely related beta 1 chains are compared, residue charge is conserved in this region. These results pinpoint the central region as a focus of functional divergence among integrin beta chains, perhaps relating to the ability of each beta integrin class to associate with a specific array of alpha integrins. Furthermore, they imply that positive, directional selection on this region has occurred in the evolution of the integrin beta-chain gene family.
Mol Biol Evol 1992 Mar
PMID:Coevolution of the vertebrate integrin alpha- and beta-chain genes. 156 Jul 59

Chitin, the beta 1,4-linked polymer of N-acetylglucosamine, is a fibrous polysaccharide that in many yeasts helps to maintain the structure of the mother-bud junction and in filamentous fungi is often the major supporting component of the cell wall. We have previously described a Candida albicans chitin synthase, CHS1. The DNA and derived protein sequences of a second gene, CHS2, are presented and compared with previously published gene sequences. Northern blot analysis shows that strikingly different levels of synthase 1 and 2 expression occur during yeast and hyphal phases of Candida growth.
Mol Microbiol 1992 Feb
PMID:Expression of chitin synthase genes during yeast and hyphal growth phases of Candida albicans. 156 Jul 78

Mutations in the gene encoding the human beta 1 T3 receptor (hTR beta 1) have been associated with generalized resistance to thyroid hormone (GRTH). We measured the T3-binding affinity and transcriptional regulatory capacity of the mutant hTR beta 1 from four unrelated kindreds with GRTH. These mutations are contained in different functional regions of the ligand-binding domain. The T3 affinity of the mutant receptors correlated well with the degree of impairment of their trans-activating function in a transient cotransfection system in HeLa cells; two mutant receptors with undetectable ligand affinity showed no transcriptional activity, whereas the two other mutants characterized by a 2- and 5-fold reduction in T3 affinity required 5- and 15-fold higher T3 concentrations for half-maximal activity in the cotransfection assay, respectively. All of the mutant hTR beta 1s were able to inhibit the function of transfected normal hTR beta 1 and endogenous retinoic acid receptor in activating a palindromic positive T3 response element (TRE). In the partially functional mutants this dominant negative effect could be completely reversed by increased T3 concentrations. The dominant negative potency did not depend on the type of TRE used; mutant hTR beta 1s were able to inhibit normal receptor function to the same degree on a dimer-permissive palindromic TRE as on a nondimer-permissive inverted repeat of two identical half-sites separated by five spacer bases. However, the dominant negative potency was dependent on the absolute amount of receptor expression vector transfected. The expression of normal and mutant hTR beta 1 was assessed by immunocytochemistry. The hTR beta 1 protein levels in HeLa cells paralleled the amount of transfected expression vector. Moreover, all the mutant receptors were properly expressed in the nuclei of the transfected cells. These data suggest that different mutations in the ligand-binding domain of the human hTR beta 1 result in a variable degree of functional impairment, which may partially explain the phenotypic differences between kindreds with GRTH. Our findings suggest that competition for binding to the TRE and possibly the binding of limiting accessory factors may be more important in mediating the dominant negative effect than the formation of normal/mutant T3 receptor dimers.
Mol Endocrinol 1992 Feb
PMID:Variable transcriptional activity and ligand binding of mutant beta 1 3,5,3'-triiodothyronine receptors from four families with generalized resistance to thyroid hormone. 156 68

Mutations of the thyroid hormone receptor (TR) beta 1 gene have recently been detected in several unrelated families with generalized resistance to thyroid hormone (GRTH). We now report a novel point mutation in the TR beta 1 gene in a case of a Korean-Japanese kindred. The intracellular localization and the amount of TR proteins were considered to be normal by the immunocytochemical study of cultured skin fibroblasts from the patients using anti-T3 receptor antibody. The cDNA of the T3-binding domain of the TR beta 1 gene, synthesized from the total RNA of the patients' fibroblasts, was amplified by the polymerase chain reaction, and was sequenced. A point mutation, A to G, in one allele at 1612 resulting in an amino acid substitution from lysine 438 to glutamic acid was detected. The same mutation was identified in one allele in each of the affected members. In vitro translation products of the mutant TR beta 1 gene showed decreased T3-binding activity. These data suggest that a TR mutation is predominantly responsible for GRTH, irrespective of ethnic background.
Mol Cell Endocrinol 1992 Apr
PMID:A point mutation of the T3 receptor beta 1 gene in a kindred of generalized resistance to thyroid hormone. 158 88

Preprotransforming growth factor-beta 1 (TGF beta 1) is a 390-amino acid precursor polypeptide that undergoes a number of processing steps to yield mature TGF beta 1 (amino acid residues 279-390) and a pro portion (residues 30-278) termed beta 1-latency-associated peptide (beta 1LAP). The dimeric form of beta 1LAP has been shown to associate noncovalently with the mature growth factor, resulting in inactivation of biological activity. To further characterize this interaction, the mature TGF beta 1 was radioiodinated and used to determine dissociation constants. A cross-linking method using the bifunctional covalent cross-linker bis-(sulfosuccinimidyl)suberate was found to be the best approach for measuring the amount of bound growth factor. The efficiency of cross-linking was constant within each experiment and varied between 45-55%. Saturation plots and their associated Scatchard analyses indicate apparent Kd values between 1.1-1.8 nM. Competition of TGF beta 1 binding to beta 1LAP by TGF beta 2 and TGF beta 3 (two closely related growth factors) revealed that the latter also bind beta 1LAP tightly, with apparent Kd values of 1.9 and 0.4 nM, respectively.
Mol Endocrinol 1992 May
PMID:Characterization of the binding of transforming growth factor-beta 1, -beta 2, and -beta 3 to recombinant beta 1-latency-associated peptide. 160 80


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