Disease relevance of TWF1

• The interactions of three singly substituted peptide variants of the HTLV-1 Tax peptide bound to HLA-A2 with the A6 T cell receptor have been studied using T cell assays, kinetic and thermodynamic measurements, and X-ray crystallography [1].
• Effect of a novel octapeptide urokinase fragment, A6, on experimental choroidal neovascularization in the monkey [2].
• Further work is indicated to evaluate the potential role of A 6 in therapy for human CNV associated with age-related macular degeneration [2].
• CONCLUSIONS: Intravitreal A 6 injections effectively inhibited CNV in cynomolgus monkeys without evidence of toxicity [2].

High impact information on TWF1

• Conversely, replacement of either the asparagine at position 174 or the serine at position 176 (the first two putative carbohydrate anchorage sites in exon 7) by alanine, abrogated the reactivity of the A6 mAb, but not that of the UCHL1 mAb [3].
• Replacement of the threonine residue at position 8 (last amino acid encoded in exon 3 and a putative O-linked carbohydrate anchorage site) by an alanine, completely abrogated the reactivity of the UCHL1 mAb, but did not affect that of the A6 mAb [3].
• Taken together, these results demonstrate that twinfilin is a novel, highly conserved actin monomer-sequestering protein involved in regulation of the cortical actin cytoskeleton [4].
• A clone, designated A6, contained a 3-kb cDNA insert with a predicted open reading frame of 350 amino acids [5].
• Thus, A6 represents a novel tyrosine kinase which is highly divergent from previously described members of this important class of regulatory molecules [5].

Biological context of TWF1

• DNA sequence analysis failed to reveal any detectable similarity with previously known genes, and the predicted A6 protein lacked any of the motifs commonly conserved in the catalytic domains of protein kinases [5].
• Mutations in the twinfilin gene result in defects in the bipolar budding pattern in S. cerevisiae and in a rough eye phenotype and aberrant bristle morphology in Drosophila melanogaster [6].
• Mammals have two twinfilin isoforms whose subcellular localizations and tissue distributions are differentially regulated [7].
• Isolated ADF-H domains associate with ADP-G-actin with rapid second-order kinetics, whereas the association of wild-type twinfilin with G-actin exhibits kinetics consistent with a two-step binding process [8].
• Activation of Na+-permeant cation channel by stretch and cyclic AMP-dependent phosphorylation in renal epithelial A6 cells [9].

Anatomical context of TWF1

• Perivascular mononuclear inflammatory cells, reactive astrocytes and macrophages expressed ephrin A1-4, Eph A1, -A3, -A4, -A6 and -A7 in active MS lesions [10].
• Insulin-like growth factor-I also activated reconstituted ENaC and increased Na(+) reabsorption across renal A6 epithelial cell monolayers via PI3K [11].
• Human erythrocyte nucleoside-diphosphate kinase (NDP kinase) is a hexameric enzyme consisting of two kinds of polypeptide chains, A and B. By random association (A6, A5B...AB5, B6) these polypeptides form isoenzymes differing in their isoelectric point [12].
• To establish that the stimulation of the PI 3-kinase signaling cascade is causing stimulation of apical epithelial Na channel, we added permeant forms of phosphatidylinositol (PI) phosphate (P) derivatives complexed with a histone carrier to A6 epithelium [13].
• Tyrosine-hydroxylase-positive neurons in the dorsolateral pontine tegmentum (A4, A6, and A7--the locus coeruleus complex) of the ferret are rather diffusely distributed, as has been observed in other carnivore species such as the cat and the dog, but unlike the cat, these cells in the ferret display a relative uniformity in size and morphology [14].

Associations of TWF1 with chemical compounds

• The apical membrane of confluent monolayers of A6 cells expressed a 29-pS channel, which was activated by stretch or by 3-isobutyl-1-methylxanthine (IBMX), an inhibitor of phosphodiesterase [9].
• Phosphatidylinositol 3,4,5-trisphosphate: an early mediator of insulin-stimulated sodium transport in A6 cells [13].
• By Western blot analysis of A6 cell extracts, the inositol 3-phosphatase PTEN and the protein kinase B PKB were both detected [13].
• The apical membrane of distal nephron epithelium (A6) has a Ca(2+)-dependent outwardly rectifying Cl- channel with single channel conductances of 3 pS for outward current and 1 pS for inward current under the basal condition [15].
• We found that incubation of A6 cell microsomes from dexamethasone-induced cells with antibodies against family 3A proteins specifically inhibited corticosterone 6 beta-hydroxylase activity [16].

Analytical, diagnostic and therapeutic context of TWF1

• Blocker-induced noise analysis and laser scanning confocal microscopy were used to test the idea that cAMP-mediated vesicle exocytosis/endocytosis may be a mechanism for regulation of functional epithelial Na+ channels (ENaCs) at apical membranes of A6 epithelia [17].
• Furthermore, A6 RNA hybridized with 3A cDNAs on Northern blots and genomic DNA from A6 cells hybridized with a 3A cDNA on a Southern blot [16].

References