PubMed Health⌕ Search

Biomedical subjects

Marcus Quack

Publications and source records attributed to Marcus Quack.

2 recordsLinked to original sources

A novel Syk-family tyrosine kinase from Schistosoma mansoni which is preferentially transcribed in reproductive organs.

The complete coding deoxyribonucleic acid for a novel tyrosine kinase (TK) of the human parasite Schistosoma mansoni has been cloned and characterized. The molecule was designated TK4. The sequence predicts a translation product of about 140 kDa containing two Src homology 2 domains and a tyrosine kinase domain. Data base analyses indicate that TK4 belongs to the Syk family of TKs which has not been identified in schistosomes or other Acoelomata yet. The presence of a member of the Syk family in this phylum supports previous findings demonstrating that TK subclasses were established early in evolution. Although Northern blot and reverse transcription polymerase chain reaction analyses show transcription of TK4 in larval stages and adult schistosomes of both genders, TK4 is more abundantly transcribed in males. In situ hybridization data demonstrate the gender-independent occurrence of TK4 transcripts in parenchymatic cells. Significant signals were detected in the oocytes of the female and in the spermatocytes of the male suggesting that TK4, among other functions, may play a role in germ cell development. This is an unexpected finding considering that Syk-family TKs of invertebrates and vertebrates described so far are not involved in the differentiation of the gonads.

Amino Acid Sequence↗

Differential nuclear receptor signalling from DR4-type response elements.

Nuclear receptors form a large family of highly related transcription factors that transform an incoming signal in the form of a lipophilic hormone into an activation of the basal transcriptional machinery. The specific recognition of nuclear receptor DNA binding sites, referred to as response elements (REs), determines the genes that can be regulated by nuclear hormones. In this study, it was shown that the complexes of the retinoid X receptor (RXR) with either the vitamin D3 receptor (VDR), the thyroid hormone receptor (T3R) or the liver X receptor (LXR) have comparable functionality on a RE of the rat pit-1 gene that is formed by a direct repeat of two hexameric binding motifs spaced by 4 nucleotides (DR4). The sequence of two nucleotides 5'-flanking the downstream binding motif of this DR4-type RE and, interestingly, also those flanking the upstream motif were shown to have in part rather drastic and receptor-specific effects on heterodimer complex formation on DNA. In particular, a downstream substitution into GA reduced the complex formation for LXR specifically, while upstream substitutions into AA or TA increase complex formation for LXR and, to a lesser extent, T3R. The preference of this in vitro complex formation was shown to correlate well with the functional activity of the nuclear receptors in living cells. The results of this study allow (i) a more detailed understanding of known REs, (ii) a more straightforward search for putative REs in newly identified promoter sequences, for example, of the whole human genome, and (iii) a more precise prediction of the hormone responsiveness of the respective genes.

Animals↗