Biomedical subjects

Xiaofei Liu

Publications and source records attributed to Xiaofei Liu.

3 recordsLinked to original sources

PubMed2026

Phosphoproteomics identification of ERK-dependent activation of Rps6kb1 in cardiac hypertrophy.

Cardiomyocyte growth is tightly controlled by multiple signaling pathways. Identification of master kinases in this process is essential in exploring potential targets for the treatment of pathological cardiac hypertrophy and heart failure. Here we identified the mTOR-independent activation of ribosomal protein S6 kinase b1 (Rps6kb1) during cardiomyocyte growth. By utilizing phosphoproteomics in primary neonatal rat ventricular myocytes, we revealed Rps6kb1 as one of most activated kinases under growth stimulation. We further demonstrated the role of Rps6kb1 phosphorylation in pathological cardiac hypertrophy and heart failure. We showed that the phosphorylation of multiple sites in Rps6kb1, including T367 in the kinase domain and S418/T421/S424 in the C-terminal domain, is not directly regulated by the activity of mTOR but coupled with the activation of the MEK1/ERK axis. In mice, cardiomyocyte-specific deletion of Rps6kb1 significantly inhibited both constitutively active ERK- and pressure overload-induced cardiac hypertrophy. In contrast, cardiomyocyte-specific overexpression of wild-type Rps6kb1, rather than the phosphorylation-defective mutant, elevated cardiac hypertrophy and augmented pressure overload-induced heart failure. In conclusion, our findings reveal that the MEK/ERK axis primes Rps6kb1 activation through phosphorylation of 2 separate domains of Rps6kb1, which may play an essential role in cardiac hypertrophy and heart failure under hemodynamic stress.

Animals↗

PubMed2006

Large-scale chemoenzymatic synthesis of blood group and tumor-associated poly-N-acetyllactosamine antigens.

Poly-N-acetyllactosamines (pLNs) are common terminal sugars of many N- and O-linked glycan structures present in glycoproteins and glycolipids. Utilizing various glycosyltransferases, we developed new and efficient chemoenzymatic methods for the synthesis of pLNs in gram-scale. Specifically, the use of sialyltransferases and fucosyltransferases enabled us to synthesize and purify 24 blood group and tumor-associated pLN derivatives with alpha-(2-->3)- and alpha-(2-->6)-linked sialic acid, as well as with alpha-(1-->2)- and alpha-(1-->3)-linked fucose. All synthesized derivatives were linked to a short 2-azidoethyl spacer for further modification.

Antigens, Neoplasm↗

PubMed2006

A novel scoring schema for peptide identification by searching protein sequence databases using tandem mass spectrometry data.

BACKGROUND: Tandem mass spectrometry (MS/MS) is a powerful tool for protein identification. Although great efforts have been made in scoring the correlation between tandem mass spectra and an amino acid sequence database, improvements could be made in three aspects, including characterization ofpeaks in spectra, adoption of effective scoring functions and access to thereliability of matching between peptides and spectra. RESULTS: A novel scoring function is presented, along with criteria to estimate the performance confidence of the function. Through learning the typesof product ions and the probability of generating them, a hypothetic spectrum was generated for each candidate peptide. Then relative entropy was introduced to measure the similarity between the hypothetic and the observed spectra. Based on the extreme value distribution (EVD) theory, a threshold was chosen to distinguish a true peptide assignment from a random one. Tests on a public MS/MS dataset demonstrated that this method performs better than the well-known SEQUEST. CONCLUSION: A reliable identification of proteins from the spectra promises a more efficient application of tandem mass spectrometry to proteomes with high complexity.

Algorithms↗