Biomedical subjects

Sheng Ma

Publications and source records attributed to Sheng Ma.

5 recordsLinked to original sources

PubMed2003

Role of Plk2 (Snk) in mouse development and cell proliferation.

Plk2 (Snk) is a polo-like kinase expressed at G(1) in cultured cells and mainly in the hippocampal neurons in the brains of adult rodents, but its function is poorly understood. We have generated mice deficient in Plk2 by gene targeting. Although Plk2 is not required for postnatal growth, Plk2(-/-) embryos show retarded growth and skeletal development late in gestation. The labyrinthine zone of the placenta is diminished in Plk2(-/-) embryos due to decreased cell proliferation. Cultured Plk2(-/-) embryonic fibroblasts grow more slowly than normal cells and show delayed entry into S phase. These data suggest a role for Plk2 in the cell cycle.

Animals↗

PubMed2003

The serum-inducible protein kinase Snk is a G1 phase polo-like kinase that is inhibited by the calcium- and integrin-binding protein CIB.

Identified as an immediate-early transcript, the serum-inducible kinase Snk bears sequence homology with the polo-like kinases. Endogenous Snk was detected in early G(1) in NIH 3T3 cells, and nascent Snk showed a half-life of about 15 min. The kinase activity of endogenous Snk was detected in G(1). Substitution of Thr-236 with a glutamate residue increased Snk kinase activity by about 10-fold, whereas substitution of Lys-108 abolished its kinase activity. Disrupting the polo-box did not significantly change Snk kinase activity. A GFP-C-Snk fusion protein showed polo-box-dependent localization to the microtubule organizing center, and ectopic expression of Snk in COS-7 cells induced changes in cell morphology, depending on Snk kinase activity and the polo-box. The capacity of Snk to induce morphological changes was inhibited by the calcium- and integrin-binding protein CIB. CIB co-immunoprecipitated with Snk and inhibited the kinase activity of Snk, suggesting that CIB is a negative regulator for Snk kinase activity.

3T3 Cells↗

PubMed2002

Phosphorylation of threonine 210 and the role of serine 137 in the regulation of mammalian polo-like kinase.

The mammalian polo-like kinase (Plk) plays a critical role in M-phase progression. Plk is phosphorylated and activated by an upstream kinase(s), which has not yet been identified in mammalian cells. Phosphopeptide mapping and phosphoamino acid analyses of Plk labeled in vivo and phosphorylated in vitro by Xenopus polo-like kinase kinase-1 (xPlkk1) or by lymphocyte-oriented kinase, its most closely related mammalian enzyme, indicate that Thr-210 is a major phosphorylation site in activated Plk from mitotic HeLa cells. Although the amino acid sequence surrounding Ser-137 is similar to that at Thr-210 and is conserved in Plk family members, Ser-137 is not detectably phosphorylated in mitotic mammalian cells or by xPlkk1 in vitro. Nevertheless, the substitution of either Thr-210 or Ser-137 with Asp (T210D or S137D) elevates the kinase activity of Plk. The kinase activity of the double mutant S137D/T210D is not significantly different from that of T210D or S137D, demonstrating that substitution of both residues does not have an additive effect on Plk activity. Expression of the S137D mutant construct arrested HeLa cells in early S-phase with slightly separated centrosomes, whereas cells expressing wild type and T210D were arrested or delayed in M-phase. These data indicate that the Ser-137 may have an unexpected and novel role in the function of Plk.

Animals↗

PubMed2002

Functional studies on the role of the C-terminal domain of mammalian polo-like kinase.

Mammalian polo-like kinase (Plk) acts at various stages in early and late mitosis. Plk is phosphorylated and activated in mitosis, and the proper subcellular localization of Plk is essential for mitotic regulation. We have observed that overexpression of the C-terminal domain of Plk is more effective than wild-type or kinase-defective Plk in causing mitotic delay or arrest. The specific activity of Plk with C-terminal deletions or substitution of aspartate for threonine-210 is increased severalfold relative to wild type. We show in this communication that the C-terminal domain can bind to full-length or the catalytic domain of Plk and inhibit its kinase activity, and that this binding is disrupted when threonine-210 is substituted with an aspartic acid residue. The C-terminal domain binds unphosphorylated Plk from G(2) arrested cells, but not phosphorylated Plk from mitotic cells. Green fluorescent protein-C-terminal Plk is localized at the centrosome and the midbody of transfected cells as shown previously for full-length enzyme. These and other data indicate that although the C terminus serves to regulate Plk kinase activity, the localization of the C terminus at the centrosome and other sites in transfected cells may block the correct localization of endogenous Plk.

Animals↗

PubMed1997

An Efficient EM-based Training Algorithm for Feedforward Neural Networks.

A fast training algorithm is developed for two-layer feedforward neural networks based on a probabilistic model for hidden representations and the EM algorithm. The algorithm decomposes training the original two-layer networks into training a set of single neurons. The individual neurons are then trained via a linear weighted regression algorithm. Significant improvement on training speed has been made using this algorithm for several bench-mark problems. Copyright 1997 Elsevier Science Ltd. All Rights Reserved.

Journal Article↗