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)

We have examined the influence of transforming agents on the in vitro modulation of the 90 kDa heat-shock protein (hsp-90) associated with the calf uterine progesterone receptor (PR). This analysis was facilitated by the use of alpha PR6 (Sullivan et al. 1986) (anti-PR monoclonal antibody that recognizes 110 kDa protein of chicken PR, subunit PR-B), which was seen to shift the rate of sedimentation of the untransformed (8S) and thermally transformed (4S) [3H]R5020-receptor complexes from the calf uterine cytosol toward the bottom of the tube. Silver staining of the alpha PR6-purified calf uterine cytosol revealed the presence of two major proteins with Mr 114 kDa and 90 kDa. Affinity-labeling of uterine cytosol with [3H]R5020, however, yielded only one major protein of 114 kDa. Incubation of uterine cytosol with AC88 (Riehl et al. 1985), a monoclonal antibody that recognizes hsp-90, resulted in a precipitation of a single 90 kDa protein which showed electrophoretic mobility similar to the second protein precipitated with alpha PR6. Western blot analysis confirmed that alpha PR6 interacts only with the 114 kDa cytosol protein representing the calf uterine PR. Incubation of PR complexes at 23 degrees C or at 0 degrees C with 0.3 M KCl or 10 mM ATP also caused the dissociation of hsp-90 from the 114 kDa PR protein, although thermal transformation was less effective in dissociating hsp-90 from PR when the ligand binding site was occupied by the antiprogestin RU486. The presence of iodoacetamide (IA) stabilized the nontransformed RU486-bound PR against thermal transformation while there was dissociation of hsp-90 from the R5020-receptor complexes. Results of our study demonstrate that calf uterine PR is represented by a major steroid binding protein of 114 kDa that exists in association with hsp-90. Exposure to transforming conditions leads to dissociation of receptor-associated hsp-90. Furthermore, the inability of IA-treated RU486-occupied PR to transform suggests that transformation of agonist-bound PR involves SH-groups which must be protected from the inactivating influence of IA.
Mol Cell Biochem 1991 Jun 26
PMID:Immunoanalysis of calf uterine progesterone receptor: modulation of receptor-associated 90 kDa heat-shock protein. f. 192 9

We showed previously that transformation by cytoplasmic and membrane-associated oncogenes including ras results in uncoupling between surface stimulation by platelet-derived growth factor, bombesin, and serum and activation of intracellular phospholipase C (PLC); this uncoupling does not involve alterations at the receptor or effector enzyme levels (T. Alonso, R. O. Morgan, J. C. Marvizon, H. Zarbl, and E. Santos, Proc. Natl. Acad. Sci. USA 85:4271-4275, 1988). In this study, we stimulated normal and oncogene-transformed NIH 3T3 cells with fluoroaluminate (AIF4-), thus directly activating PLC-associated G protein(s) and bypassing the receptor step. A1F4(-)-elicited PLC responses were significantly impaired in transformed cells when compared with those in their normal counterparts, suggesting that the uncoupling of PLC is the result, at least in part, of functional impairment at the G-protein level. Transformation by ras oncogenes has also been reported to result in enhanced PLC response to bradykinin resulting from increased receptor numbers (G. Parries, R. Hoebel, and E. Racker, Proc. Natl. Acad. Sci. USA 84:2648-2652, 1987; J. Downward, J. de Gunzburg, R. Riehl, and R. Weinberg, Proc. Natl. Acad. Sci. USA 85:5774-5778, 1988). We demonstrate here that transformation by other membrane-associated and cytoplasmic oncogenes also results in increased responsiveness to bradykinin ("supercoupling") and enhanced receptor numbers. However, there is no direct correlation between the number of receptors and the enhancement in responsiveness, suggesting that other factors besides receptor number are also involved in the enhanced responses. We propose that a common effect of transformation by cytoplasmic and membrane-associated oncogenes is functional alteration of coupling G proteins and that a similar modification of different kinds of G proteins may account for the pleiotropic alterations of signal transduction (uncoupling and supercoupling) observed.
Mol Cell Biol 1990 Jun
PMID:Alterations of G-protein coupling function in phosphoinositide signaling pathways of cells transformed by ras and other membrane-associated and cytoplasmic oncogenes. 216 May 94

Riehl's melanosis is a hyperpigmentary disorder that occurs predominantly on the face and neck. To date, the pathogenesis of Riehl's melanosis with regards to the melanogenic properties and paracrine melanogenic molecules has not well been studied. This study was aimed to provide a novel perspective on the pathogenesis of Riehl's melanosis by identifying the relevant paracrine melanogenic molecules in Riehl's melanosis. Skin biopsies were performed on lesional and normal-appearing perilesional skin of 12 patients with Riehl's melanosis and 12 age- and sex-matched healthy controls. Histopathological and immunohistochemical staining for paracrine melanogenic molecules was analyzed. The major histopathological findings of Riehl's melanosis were basal hyperpigmentation, melanocyte proliferation, interface change, dermal pigmentary incontinence, vascular proliferation, and dermal inflammation. Dermal expression intensities of stem cell factor (SCF) and c-kit were increased in the lesional skin of Riehl's melanosis. In addition, increased expression of epidermal and dermal ET-1 was also observed in the lesional skin of Riehl's melanosis. Increased tissue expressions of SCF, c-kit, and ET-1 in Riehl's melanosis support the role of these paracrine melanogenic molecules in the pathogenesis of Riehl's melanosis. The findings from this study might present useful information on the pathogenetic mechanism of Riehl's melanosis.
Int J Mol Sci 2020 Mar 02
PMID:Melanogenic Properties and Expression Profiles of Melanogenic Paracrine Molecules in Riehl's Melanosis. 3212 26