Biomedical subjects

Zhiqin Li

Publications and source records attributed to Zhiqin Li.

5 recordsLinked to original sources

PubMed2007

Identification of SH2B2beta as an inhibitor for SH2B1- and SH2B2alpha-promoted Janus kinase-2 activation and insulin signaling.

The SH2B family has three members (SH2B1, SH2B2, and SH2B3) that contain conserved dimerization (DD), pleckstrin homology, and SH2 domains. The DD domain mediates the formation of homo- and heterodimers between members of the SH2B family. The SH2 domain of SH2B1 (previously named SH2-B) or SH2B2 (previously named APS) binds to phosphorylated tyrosines in a variety of tyrosine kinases, including Janus kinase-2 (JAK2) and the insulin receptor, thereby promoting the activation of JAK2 or the insulin receptor, respectively. JAK2 binds to various members of the cytokine receptor family, including receptors for GH and leptin, to mediate cytokine responses. In mice, SH2B1 regulates energy and glucose homeostasis by enhancing leptin and insulin sensitivity. In this work, we identify SH2B2beta as a new isoform of SH2B2 (designated as SH2B2alpha) derived from the SH2B2 gene by alternative mRNA splicing. SH2B2beta has a DD and pleckstrin homology domain but lacks a SH2 domain. SH2B2beta bound to both SH2B1 and SH2B2alpha, as demonstrated by both the interaction of glutathione S-transferase-SH2B2beta fusion protein with SH2B1 or SH2B2alpha in vitro and coimmunoprecipitation of SH2B2beta with SH2B1 or SH2B2alpha in intact cells. SH2B2beta markedly attenuated the ability of SH2B1 to promote JAK2 activation and subsequent tyrosine phosphorylation of insulin receptor substrate-1 by JAK2. SH2B2beta also significantly inhibited SH2B1- or SH2B2alpha-promoted insulin signaling, including insulin-stimulated tyrosine phosphorylation of insulin receptor substrate-1. These data suggest that SH2B2beta is an endogenous inhibitor of SH2B1 and/or SH2B2alpha, negatively regulating insulin signaling and/or JAK2-mediated cellular responses.

Adaptor Proteins, Signal Transducing↗

PubMed2004

[Purification and characteristics of polypeptide with inhibition of platelet aggregation from Agkistrodon blomhoffii Bioe].

A polypeptide, SV-PP-2, was purified from Agkistrodon blomhoffii Bioe by HPLC C18 column. The SV-PP-2 has molecular weight of 23339.00 Da, and can inhibit the ADP-induced platelet aggregation in dose-dependent manner. There have been no such polypeptides reported yet which has inhibition of platelet aggregation and similar molecular weight to SV-PP-2.

Agkistrodon↗

PubMed2004

[Purification of small peptide from Agkistrodon blomhoffii Bioe and its inhibition on platelet aggregation].

This is the first report to purify a new peptide SV-PP-1 from Agkistrodon blomhoffii Bioe. SV-PP-1 has molecular weight of 1234.616 Da and can inhibit on platelet aggregation. SV-PP-1 significantly inhibited the ADP-induced platelet aggregation. It has been found up to now that SV-PP-1 is the smallest peptide inhibiting on platelet aggregation from snake venom.

Agkistrodon↗

PubMed2003

Identification of a nuclear protein that promotes NF-kappaB activation.

Receptor-interacting protein (RIP) is a serine/threonine protein kinase that is critically involved in tumor necrosis factor receptor-1 (TNF-R1)-induced NF-kappaB activation. In a yeast two-hybrid screening for potential RIP-interacting proteins, we identified a novel protein designated as NKAP. Although NKAP interacts with RIP in yeast, NKAP does not interact with RIP in mammalian cells in co-immunoprecipitation experiments. When overexpressed in 293 cells, NKAP activated NF-kappaB in a dose-dependent manner. Moreover, down-regulation of NKAP by antisense RNA significantly inhibited TNF- and IL-1-induced NF-kappaB activation. Immunofluorescent staining indicated that NKAP was localized in the nucleus. Our findings suggest that NKAP is a novel nuclear regulator of TNF- and IL-1-induced NF-kappaB activation.

Amino Acid Sequence↗

PubMed2003

Casper/c-FLIP is physically and functionally associated with NF-kappaB1 p105.

Casper/c-FLIP is a caspase-8-related molecule critically involved in regulation of death receptor-induced apoptosis. It has been shown that Casper can either promote or antagonize apoptosis and can activate the transcription factor NF-kappaB. The exact functions of Casper are controversial. To further understand how Casper signals, we searched Casper-interacting proteins by yeast two-hybrid screening. This effort identified NF-kappaB1 (p105), an atypical IkappaB molecule and the precursor of NF-kappaB subunit p50. Co-immunoprecipitation experiments indicated that Casper interacted with p105 in 293 cells and this interaction was mediated through the C-terminal IkappaB-like domain (IkappaBgamma). Overexpression of p105 and IkappaBgamma inhibited Casper-induced NF-kappaB activation and potentiated Casper-induced apoptosis. Furthermore, Casper and its C-terminal caspase-like domain inhibited p105 processing into p50. Our findings suggest that p105 is involved in Casper-mediated regulation of apoptosis and NF-kappaB activation.

CASP8 and FADD-Like Apoptosis Regulating Protein↗