Disease relevance of Krt2-5

• However, differential expression of genes, especially cytokeratins (CK8 and CK5) and collagens (III and IV) between highly metastatic and low metastatic rat mammary adenocarcinoma cell lines might initiate further investigation of these genes in metastatic process [1].

High impact information on Krt2-5

• Rat keratin K5 and vimentin complementary DNAs have been isolated, identified, and used to study keratin and vimentin expression as markers for cell differentiation [2].
• Herein, we demonstrate that mouse and rat spermatids assemble in the subacrosomal space a cytoskeletal scaffold containing F-actin and Sak57, a keratin ortholog [3].
• K5 reduced vascular permeability at doses substantially lower than that required for inhibition of retinal neovascularisation [4].
• Previously we have shown that plasminogen kringle 5 (K5), an angiogenic inhibitor, inhibits retinal neovascularisation in the rat model of oxygen-induced retinopathy (OIR) [4].
• Moreover, K5 inhibited IGF-1-induced hyperpermeability, which is known to arise through up-regulation of endogenous VEGF expression [4].

Biological context of Krt2-5

• The K5-induced reduction in vascular permeability correlated with its down-regulation of VEGF expression in the retina [4].
• Total protein and mRNA levels of cytokeratins 8, 18, c-CAM 105 (the calcium-independent cell adhesion molecule) and Z0-1, as detected by western and/or northern blot analyses, respectively, are induced, while cytokeratin 5 and 15 are lost, and occludin is unchanged [5].
• The transfer of the MT oncogene into the keratinocytes did not result in the loss of CK5/CK14 IFs nor the inhibition of CK14 gene expression [6].
• Results of this work, together with previous observations during spermiogenesis, show that Sak 57 associates with cytoplasmic microtubules in a timely fashion [7].
• Sak57 displays conserved amino acid sequences found in the 1A and 2A regions of the alpha-helical rod domain of keratins in human, rat, and mouse [8].

Anatomical context of Krt2-5

• Gap junctions in undifferentiated epithelial cells at days 1-10 of life were composed of Cx 43, which always colocalized with basal cell cytokeratins (CK 5/15) [9].
• Confocal laser scanning microscopy was used to analyze the three-dimensional arrangement of Sak57 in pachytene spermatocytes [10].
• Rat sperm tail samples displayed only the Sak57 detergent-insoluble form and its pl was more acidic (4.7-4.8) [10].
• Immunogold electron microscopy confirmed the presence of Sak57 immunoreactivity among microtubules of the manchette and on outer dense fibers and the longitudinal columns linking the ribs of the fibrous sheath [8].
• We have found that rat testis displays two immunoreactive proteins: a soluble 83 kDa protein with pl range 5.9-6.3, regarded as a precursor, and both detergent-insoluble and soluble 57 kDa protein with pl range 5.0-5.9, corresponding to the mature form Sak57 [10].

Associations of Krt2-5 with chemical compounds

• RESULTS: Two types of cell populations, a large single-cell population and a small single-cell population, were obtained and characterized as basal and luminal epithelial cells by immunostaining for cytokeratin 5 and cytokeratin 8, respectively [11].
• Anti-MAP sera were used for further analysis of the biochemical characteristics of Sak57 in testis and sperm tails using chromatofocusing, immunoblotting, and [32P] orthophosphate-labeling [10].
• We have purified a 57 kDa protein (designated Sak57, for spermatogenic cell/sperm-associated keratin) from sodium dodecyl sulfate-beta-mercaptoethanol (SDS-beta ME)-dissociated outer dense fibers isolated from rat sperm tails [10].
• RESULTS: Subcutaneous, intraperitoneal, subconjunctival, and retrobulbar injections and topical eyedrop application of K5 significantly reduced retinal vascular permeability in both the OIR and STZ-diabetic rat models [12].

Other interactions of Krt2-5

• We now report indirect immunofluorescence, confocal laser scanning microscopy and immunogold electron microscopy data showing that Sak57 is associated with the microtubular mantie of the manchette, a transient microtubular structure largely regarded as formed by tubulin and microtubule-associated proteins [8].
• In the AP keratin 14 was basally localized by 1 day postnatal but keratin 5 and 7 did not colocalize to the basal cells until days 9 and 12, respectively [13].

Analytical, diagnostic and therapeutic context of Krt2-5

• Intravitreal injection of K5, reduced vascular permeability in both animal models, but did not affect permeability in normal rats [4].
• Internal protein sequence analysis of Sak 57 revealed 70-100% homology to the 1A and 2A regions of the alpha-helical rod domain of human, mouse, and rat keratins [7].
• Indirect immunofluorescence was used to determine the localization of Sak57 in isolated outer dense fibers, epididymal sperm, spermatids, and pachytene spermatocytes [10].

References