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Cai Huang

Publications and source records attributed to Cai Huang.

6 recordsLinked to original sources
PubMed2026

Systematic Genome Mining of Peptide Metallophore Pathways Uncovers Novel Dibenzo-α-Pyrone Siderophores in Streptomyces sp. HB-R818.

Metallophores are metal-chelating natural products that enable microorganisms to acquire essential metal ions and mediate processes such as iron uptake, quorum sensing, and interspecies competition. Metallophores also display potent antimicrobial and anticancer activities, highlighting their biomedical and biotechnological potential. Despite Streptomyces being prolific producers of bioactive metabolites, their metallophore pathways remain largely unexplored. Here, we systematically mined 519 reference Streptomyces genomes to elucidate the distribution, diversity, and structural features of metallophores and identified a new metallophore biosynthetic gene cluster (BGC) (ser) from sponge-derived Streptomyces sp. HB-R818. Using a metabologenomics-based strategy, five new siderophore analogs serobactins A-E (1-5) and known enterobactin (6) were isolated. These compounds show potential to inhibit tumor invasion and feature a unique dibenzo-α-pyrone scaffold in structure, formed through the cyclization of an extra 2,3-dihydroxybenzoic acid with 2,3-dihydroxybenzoyl serine. The BGC (ser) was validated by the nonribosomal peptide synthetase gene knockout; the biosynthesis of 1-6 was proposed.

Siderophores↗
PubMed2004

MAP kinases and cell migration.

Recent studies have demonstrated that mitogen-activated protein kinases (MAPKs), including Jun N-terminus kinase (JNK), p38 and Erk, play crucial roles in cell migration. JNK, for example, regulates cell migration by phosphorylating paxillin, DCX, Jun and microtubule-associated proteins. Studies of p38 show that this MAPK modulates migration by phosphorylating MAPK-activated protein kinase 2/3 (MAPKAP 2/3), which appears to be important for directionality of migration. Erk governs cell movement by phosphorylating myosin light chain kinase (MLCK), calpain or FAK. Thus, the different kinases in the MAPK family all seem able to regulate cell migration but by distinct mechanisms.

Animals↗
PubMed2004

Phosphorylation of paxillin by p38MAPK is involved in the neurite extension of PC-12 cells.

Cell adhesions play an important role in neurite extension. Paxillin, a focal adhesion adaptor protein involved in focal adhesion dynamics, has been demonstrated to be required for neurite outgrowth. However, the molecular mechanism by which paxillin regulates neurite outgrowth is unknown. Here, we show that paxillin is phosphorylated by p38MAPK in vitro and in nerve growth factor (NGF)-induced PC-12 cells. Ser 85 (Ser 83 for endogenous paxillin) is identified as one of major phosphorylation sites by phosphopeptide mapping and mass spectrometry. Moreover, expression of the Ser 85 --> Ala mutant of paxillin (paxS85A) significantly inhibits NGF-induced neurite extension of PC-12 cells, whereas expression of wild-type (wt) paxillin does not influence neurite outgrowth. Further experiments indicate that cells expressing paxS85A exhibit small, clustered focal adhesions which are not normally seen in cells expressing wt paxillin. Although wt paxillin and paxS85A have the same ability to bind vinculin and focal adhesion kinase, wt paxillin more efficiently associates with Pyk2 than paxS85A. Thus, phosphorylation of paxillin is involved in NGF-induced neurite extension of PC-12 cells, probably through regulating focal adhesion organization.

Animals↗
PubMed2004

A role for JNK-paxillin signaling in cell migration.

Recently, we and others demonstrated that JNK is essential for cell migration in a number of cell types. We also showed that JNK phosphorylates serine 178 on paxillin, a focal adhesion adaptor, both in vitro and in vivo. Moreover, phosphorylation of Ser 178 on paxillin is essential for cell migration and involved in modulating cell adhesions. A model is proposed to depict the role of JNK-paxillin signaling in cell migration.

Animals↗
PubMed2003

JNK phosphorylates paxillin and regulates cell migration.

The c-Jun amino-terminal kinase (JNK) is generally thought to be involved in inflammation, proliferation and apoptosis. Accordingly, its substrates are transcription factors and anti-apoptotic proteins. However, JNK has also been shown to be required for Drosophila dorsal closure, and MAP kinase/ERK kinase kinase 1, an upstream kinase in the JNK pathway, has been shown to be essential for cell migration. Both results imply that JNK is important in cell migration. Here we show that JNK1 is required for the rapid movement of both fish keratocytes and rat bladder tumour epithelial cells (NBT-II). Moreover, JNK1 phosphorylates serine 178 on paxillin, a focal adhesion adaptor, both in vitro and in intact cells. NBT-II cells expressing the Ser 178 --> Ala mutant of paxillin (Pax(S178A)) formed focal adhesions and exhibited the limited movement associated with such contacts in both single-cell-migration and wound-healing assays. In contrast, cells expressing wild-type paxillin moved rapidly and retained close contacts as the predominant adhesion. Expression of Pax(S178A) also inhibited the migration of two other cell lines. Thus, phosphorylation of paxillin by JNK seems essential for maintaining the labile adhesions required for rapid cell migration.

Amino Acid Sequence↗
PubMed2002

Pseudo-MS3 in a MALDI orthogonal quadrupole-time of flight mass spectrometer.

Both the matrix selected and the laser fluence play important roles in MALDI-quadrupole/time of flight (QqTOF) fragmentation processes. "Hot" matrices, such as alpha-cyano4-hydroxycinnamic acid (HCCA), can increase fragmentation in MS spectra. Higher laser fluence also increases fragmentation. Typical peptide fragment ions observed in the QqTOF are a, b, and y ion series, which resemble low-energy CID product ions. This fragmentation may occur in the high-pressure region before the first mass-analyzing quadrupole. Fragment ions can be selected by the first quadrupole (Q1), and further sequenced by conventional MS/MS. This allows pseudo-MS3 experiments to be performed. For peptides of higher molecular weight, pseudo-MS3 can extend the mass range beyond what is usually accessible for sequencing, by allowing one to sequence a fragment ion of lower molecular weight instead of the full-length peptide. Peptides that predominantly show a single product ion after MS/MS yield improved sequence information when this technique is applied. This method was applied to the analysis of an in vitro phosphorylated peptide, where the intact enzymatically-generated peptide showed poor dissociation via MS/MS. Sequencing a fragment ion from the phosphopeptide enabled the phosphorylation site to be unambiguously determined.

Journal Article↗