Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

After cessation of lactation, the mammary gland undergoes involution, regressing to a state resembling that of a virgin animal. This phase of mammary gland development is characterized by epithelial cell death and tissue remodeling. To understand molecular mechanisms of mammary gland involution, we identified involution-induced clones by differential screening of a mouse mammary gland cDNA library. Several known genes were induced during mammary gland involution: sulfated glycoprotein-2 (SGP-2), WDNM1, lactoferrin, ferritin heavy chain (FHC), lysozyme and osteopontin genes. Involution of the mammary gland is presumed to be mediated by a decrease in serum prolactin level induced by weaning, but may also involve changes in paracrine or autocrine growth factors. Effects of lactogenic hormones and EGF on the expression of the involution-induced genes were examined in mammary epithelial cells. Insulin, dexamethasone, and prolactin did not influence the expression of the FHC, WDNM1 and SGP-2 genes. However, EGF strongly inhibited the expression of WDNM1 and SGP-2 genes. Our recent results are reviewed and discussed.
Int J Mol Med 1998 Jul
PMID:Gene expression during involution of mammary gland (review). 985 40

Osteopontin (OPN) is a secreted glycoprotein implicated in cell adhesion. It contains the arginine-glycine-asparatic acid (RGD) cell adhesive domain and the thrombin cleavage sequence. Although thrombin cleavage of OPN has been shown to be of physiological importance, the function of C-terminal OPN fragment cleaved by thrombin remains unknown. To determine its role, we performed cell adhesion assays using glutathione S-transferase-OPN fusion protein fragments and full-length OPN fusion protein. The N-terminal fragment containing RGD motif promoted enhanced adhesion of mouse and human fibroblasts by 2.9 and 2.8 folds in comparison with full-length OPN, respectively. The enhanced adhesion of both cells mediated by N-terminal fragment was significantly suppressed by addition of C-terminal fragment lacking RGD motif that has less cell adhesive property than full-length OPN. These results suggest that the C-terminal domain may play a pivotal role in regulating OPN functions by suppressing the RGD-dependent cell adhesion.
Biochem Mol Biol Int 1998 Dec
PMID:The carboxyl-terminal fragment of osteopontin suppresses arginine-glycine-asparatic acid-dependent cell adhesion. 989 40

PTH/PTHrP receptor gene expression was evaluated in situ in avian epiphyseal growth plates taken from normal, rachitic and tibial dyschondroplasia (TD) afflicted chicks induced by thiram or by genetic selection. In the normal growth plates, PTH/PTHrP receptor gene expression was localized to the maturation zone as demonstrated by the expression of collagen type II (col II), osteopontin (OPN) genes and alkaline phosphatase activity (AP). In TD, either induced by thiram or by genetic selection, normal levels of PTH/PTHrP receptor gene expression were observed up to 21 days post-hatch. In rickets, on the other hand, no PTH/PTHrP receptor gene expression was observed in the growth plate from day 8 of a vitamin D-deficient diet. In cultured chondrocytes, PTH caused time-dependent down-regulation of its own receptor. These results suggest that alterations in the PTH/PTHrP receptor gene expression are associated with rickets but not with TD. The reduction in the PTH/PTHrP receptor gene expression in rickets may be due to the high plasma levels of PTH.
Mol Cell Endocrinol 1999 Mar 25
PMID:Parathyroid receptor gene expression by epiphyseal growth plates in rickets and tibial dyschondroplasia. 1037 30

Rat osteoprogenitor cells were used to examine the effects of bFGF on DNA synthesis and the expression of osteoblast (OB)-related genes. bFGF, as low as 0.1 ng/ml, stimulated DNA synthesis. bFGF also increased the mRNA level of osteopontin (OP) and decreased that of type I collagen (COL I). When cultures were grown in dexamethasone (DEX) to induce OB lineage commitment, the expression of COL I, alkaline phosphatase (AP) and OP was greatly enhanced. Subsequent incubation with bFGF partially negated the stimulatory effect of DEX on AP and COL I mRNAs. bFGF also inhibited the expression of osteocalcin mRNA in cells grown in 1,25(OH)2D3 and DEX. Combined effects of bFGF with IGF-I or PDGF on DNA synthesis and OP expression were examined. bFGF + IGF-I, but not bFGF + PDGF, was more effective than PDGF alone. By comparing cells from adult and old animals, we found that bFGF-induced mitogenic activity was reduced significantly with age. In contrast, the effect of bFGF on the expression of OB genes was not significantly altered by age. These findings suggest that bFGF plays a dual role as a local positive and negative regulator on proliferation and osteogenic lineage expression, respectively, in osteoprogenitor cells, and that the mitogenic activity in response to bFGF was impaired in aging.
Mol Cell Endocrinol 1999 Apr 25
PMID:Actions of bFGF on mitogenic activity and lineage expression in rat osteoprogenitor cells: effect of age. 1041 Dec 94

The function of the most numerous cell in bone, the osteocyte, has until recently been mysterious and at times controversial. There is now an emerging consensus that osteocytes modulate signals arising from mechanical loading and so direct the appearance and disappearance of bone tissue at the microscopic level, which allows bone as an organ both to grow and to adapt efficiently to the body's mechanical needs for strength with lightness. Osteocytes appear to use some molecular signalling pathways that are familiar from other tissues, such as the generation of nitric oxide and prostaglandins as well as directing cell-cell communication via gap junctions. They may also direct the removal of damaged or redundant bone through mechanisms linked to their own apoptosis or via the secretion of specialised cellular attachment proteins such as osteopontin. Osteocytes possess receptors for parathyroid hormone/parathyroid hormone related peptide and both oestrogen receptors alpha and beta. They also express molecules which in nerve cells are involved with glutamate neuro-transmission. At least some of these receptors and their ligands may regulate osteocyte apoptosis and modulate osteocyte signalling.
Mol Cell Endocrinol 2000 Jan 25
PMID:Osteocyte function, osteocyte death and bone fracture resistance. 1068 47

The CD44 proteins form a ubiquitously expressed family of cell surface adhesion molecules involved in cell-cell and cell-matrix interactions. The multiple protein isoforms are encoded by a single gene by alternative splicing and are further modified by a range of post-translational modifications. CD44 proteins are single chain molecules comprising an N-terminal extracellular domain, a membrane proximal region, a transmembrane domain, and a cytoplasmic tail. The CD44 gene has only been detected in higher organisms and the amino acid sequence of most of the molecule is highly conserved between mammalian species. The principal ligand of CD44 is hyaluronic acid, an integral component of the extracellular matrix. Other CD44 ligands include osteopontin, serglycin, collagens, fibronectin, and laminin. The major physiological role of CD44 is to maintain organ and tissue structure via cell-cell and cell-matrix adhesion, but certain variant isoforms can also mediate lymphocyte activation and homing, and the presentation of chemical factors and hormones. Increased interest has been directed at the characterisation of this molecule since it was observed that expression of multiple CD44 isoforms is greatly upregulated in neoplasia. CD44, particularly its variants, may be useful as a diagnostic or prognostic marker of malignancy and, in at least some human cancers, it may be a potential target for cancer therapy. This review describes the structure of the CD44 gene and discusses some of its roles in physiological and pathological processes.
Mol Pathol 1999 Aug
PMID:CD44 cell adhesion molecules. 1069 38

The receptors for interleukin-3 (IL-3) and granulocyte-macrophage colony-stimulating factor (GM-CSF) share a common beta subunit, the distal cytoplasmic domain of which is essential for the promotion of cell survival by these two cytokines. Genes whose expression is specifically induced by signaling through the distal cytoplasmic domain of this receptor beta subunit were screened by a subtraction cloning approach in derivatives of a mouse pro-B-cell line. One gene thus identified was shown to encode a protein highly homologous (with only 7 amino acid substitutions) to murine osteopontin (OPN), a secreted adhesion protein. Conditioned medium from cells expressing wild-type OPN, but not that from cells expressing a deletion mutant lacking residues 79 to 140, increased the viability of a non-OPN-producing cell line in the presence of human GM-CSF. Antibody blocking experiments revealed that OPN produced as a result of IL-3 or GM-CSF signaling was secreted into the medium and, through binding to its cell surface receptor, CD44, contributed to the survival-promoting activities of these two cytokines. Furthermore, coupling of the OPN-CD44 pathway to the survival response to IL-3 was also demonstrated in primary IL-3-dependent mouse bone marrow cells. These results thus show that induction of an extracellular adhesion protein and consequent activation of its cell surface receptor are important for the antiapoptotic activities of IL-3 and GM-CSF.
Mol Cell Biol 2000 Apr
PMID:Coupling of osteopontin and its cell surface receptor CD44 to the cell survival response elicited by interleukin-3 or granulocyte-macrophage colony-stimulating factor. 1073 76

Members of the integrin family of adhesion receptors mediate both cell-cell and cell-matrix interactions and have been shown to play vital roles in embryonic development, wound healing, metastasis, and other biological processes. The integrin alpha9beta1 is a receptor for the extracellular matrix proteins osteopontin and tenacsin C and the cell surface immunoglobulin vascular cell adhesion molecule-1. This receptor is widely expressed in smooth muscle, hepatocytes, and some epithelia. To examine the in vivo function of alpha9beta1, we have generated mice lacking expression of the alpha9 subunit. Mice homozygous for a null mutation in the alpha9 subunit gene appear normal at birth but develop respiratory failure and die between 6 and 12 days of age. The respiratory failure is caused by an accumulation of large volumes of pleural fluid which is rich in triglyceride, cholesterol, and lymphocytes. alpha9(-/-) mice also develop edema and lymphocytic infiltration in the chest wall that appears to originate around lymphatics. alpha9 protein is transiently expressed in the developing thoracic duct at embryonic day 14, but expression is rapidly lost during later stages of development. Our results suggest that the alpha9 integrin is required for the normal development of the lymphatic system, including the thoracic duct, and that alpha9 deficiency could be one cause of congenital chylothorax.
Mol Cell Biol 2000 Jul
PMID:Fatal bilateral chylothorax in mice lacking the integrin alpha9beta1. 1086 76

Primary osteoblasts derived from avian long bone have been evaluated in terms of spatial and temporal expression of known osteoblastic marker proteins during the early phases of cell culture. Confocal imaging of matrix proteins revealed that osteocalcin, bone sialoprotein, osteopontin, and osteonectin were restricted to the cell interior at day 4 of culture; secretion and deposition into the extra-cellular matrix of bone sialoprotein and osteopontin was evident at 8 and 12 days of culture. Osteocalcin and osteonectin were not deposited in the matrix within the timeframe of the study. Total collagen levels produced and alkaline phosphatase activity were substantial by day 4 of culture, and increased from that point 4.0- and 5.5-fold, respectively, by culture day 12. The expression of type I collagen, PTHrP receptor, osteopontin, bone sialoprotein and osteocalcin was followed by Northern blot analysis. Type I collagen and osteopontin mRNA were expressed at constant levels throughout the culture period. Over the 12 days of culture both PTH/PTHrP receptor and bone sialoprotein mRNA expression were found to increase by 2.3- and 2.5-fold, respectively. In contrast, the expression of osteocalcin message decreased by 2.5-fold by day 8 of culture.
Comp Biochem Physiol A Mol Integr Physiol 2000 Jun
PMID:Confocal imaging and timing of secretion of matrix proteins by osteoblasts derived from avian long bone. 1093 61

Previously recognized intracellular proteins with an affinity for vitamin D metabolites include the vitamin D receptor and the cytochrome P-450-based vitamin D metabolizing mixed-function oxidases. We recently characterized a third set of high-capacity, intracellular vitamin D binding proteins (IDBPs) in the inducible heat shock protein-70 (hsp-70) family. Here we report the cloning and expression of cDNAs coding for two IDBPs. The full-length cDNAs for IDBP-1 and IDBP-2 demonstrated 95% and 94% nucleotide homology, respectively, with the cDNAs for human constitutively expressed heat shock protein 70 (hsc-70) and hsp-70. Transient expression of the IDBP cDNAs in a vitamin D-responsive primate cell line increased extractable 25-hydroxylated vitamin D metabolite-IDBP-binding 25-fold. Transfection experiments also demonstrated that the majority of the constitutively expressed 25-hydroxylated vitamin D metabolite binding activity was attributable to expression of the hsc-70-related IDBP-1 and that metabolite binding activity sublocalized to the highly conserved ATP-binding/ATPase domain of hsp-70s. Stable overexpression of IDBP-1 in wild-type cells enhanced vitamin D-directed responsiveness of endogenous vitamin D-24-hydroxylase, osteopontin, and osteocalcin genes by several-fold over that observed in cells transfected with an empty vector. These results suggest that IDBP-1 facilitates the intracellular localization of active vitamin D metabolites and vitamin D receptor-mediated transactivation.
Mol Endocrinol 2000 Sep
PMID:Intracellular vitamin D binding proteins: novel facilitators of vitamin D-directed transactivation. 1097 17


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