Identification of an Autoinhibitory Domain of p21-activated Protein Kinase 5

The p21-activated protein kinases (Paks) are serine/threonine protein kinases activated by binding to Rho family small GTPases, Rac and Cdc42. Recently, Pak family members have been subdivided into two groups, I and II. Group II Paks, including Pak4, Pak5, and Pak6, does not contain the highly conserved autoinhibitory domain that is found in the group I Paks members, i.e. Pak1, Pak2, and Pak3. In the present study, we have purified the glutathione S-transferase fusion form of Pak5 and shown for the first time that Pak5 autophosphorylation can be activated by GTP bound form of Cdc42. Mutation of histidine residues 19 and 22 to leucine on the p21-binding domain of Pak5 completely abolished the binding of Cdc42 and the Cdc42-mediated autophosphorylation. On the other hand, mutation of tyrosine 40 to cysteine of Cdc42 did not knockout the binding of Pak5. Analysis of C-terminal deletion mutants has identified an autoinhibitory fragment of Pak5 that is absent from other group II Pak family members. Taken together, these results suggest that Pak5, like Pak1, contains an autoinhibitory domain and its activity is regulated by Cdc42.postprin

Electronic transitions of platinum monoboride

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Laser spectroscopy of iridium monoboride

High resolution laser induced fluorescence spectrum of IrB in the spectral region between 545 and 610 nm has been recorded and analyzed. Reacting laser-ablated iridium atoms with 1% B2 H6 seeded in argon produced the IrB molecule. This is the first experimental observation of the IrB molecule. Four vibronic transition bands, (v,0) with v=0-3 of an electronic transition system, have been observed. Spectra of all four isotopic molecules, Ir191 B10, Ir193 B10, Ir191 B11, and Ir193 B11, were recorded. Isotopic relationships confirmed the carrier of the spectra and the vibrational quantum number assignment. Preliminary analysis of rotational lines showed that these vibronic bands are with ′ =2 and ″ =3. The electronic transition identified is assigned as the [16.5] Π23 -X Δ33 system. Partially resolved hyperfine structure which conforms to the Hund's case aΒ coupling scheme has been observed and analyzed. The bond length r0 of the lower X Δ33 state of IrB was determined to be 1.7675 Å. © 2008 American Institute of Physics.published_or_final_versio

An efficient algorithm for optimizing whole genome alignment with noise

Motivation: This paper is concerned with algorithms for aligning two whole genomes so as to identify regions that possibly contain conserved genes. Motivated by existing heuristic-based software tools, we initiate the study of an optimization problem that attempts to uncover conserved genes with a global concern. Another interesting feature in our formulation is the tolerance of noise, which also complicates the optimization problem. A brute-force approach takes time exponential in the noise level. Results: We show how an insight into the optimization structure can lead to a drastic improvement in the time and space requirement [precisely, to O(k2n2) and O(k2n), respectively, where n is the size of the input and k is the noise level]. The reduced space requirement allows us to implement the new algorithm, called MaxMinCluster, on a PC. It is exciting to see that when tested with different real data sets, MaxMinCluster consistently uncovers a high percentage of conserved genes that have been published by GenBank. Its performance is indeed favorably compared to MUMmer (perhaps the most popular software tool for uncovering conserved genes in a whole-genome scale). © Oxford University Press 2004; all rights reserved.published_or_final_versio

Coiled-coil motif as a structural basis for the interaction of HTLV type 1 Tax with cellular cofactors

Human T lymphotropic virus type 1 (HTLV-1) Tax is a multifunctional protein centrally involved in transcriptional regulation, cell cycle control, and viral transformation. The regulatory functions of Tax are thought to be mediated through protein-protein interaction with cellular cofactors. Previously we have identified several novel binding partners for Tax, including human mitotic checkpoint protein MAD1 (TXBP181), G-protein pathway suppressor GPS2 (TXBP31), and IκB kinase regulatory subunit IKK-γ. Here we described two additional Tax partners, TXBP151 and TXBP121. A closer examination of the sequences of eight independent cellular Tax-binding proteins identified by us and others revealed that all of them share a single characteristic, a highly structured coiled-coil domain. We also noted that Tax and the Tax-binding coiled-coil proteins can homodimerize. Additionally, the same domain in Tax is responsible for interaction with different coiled-coil proteins. Taken together, our findings point to a particular coiled-coil structure as one of the Tax-recognition motifs. The interaction of Tax with a particular subgroup of cellular coiled-coil proteins represents one mechanism by which Tax dysregulates cell growth and proliferation.published_or_final_versio

PAK4 phosphorylates p53 at serine 215 to promote liver cancer metastasis

PAK4 kinase contributes to signaling pathways controlling cancer cell transformation, invasion and survival, but its clinicopathological impact has begun to emerge only recently. Here we report that PAK4 overexpression in hepatocellular carcinoma (HCC) conveys aggressive metastatic properties. A novel nuclear splice isoform of PAK4 lacking exon 2 sequences was isolated as part of our studies. By stably overexpressing or silencing PAK4 in HCC cells we showed that it was critical for their migration. Mechanistic investigations in this setting revealed that PAK4 directly phosphorylated p53 at S215, which not only attenuated transcriptional transactivation activity but also inhibited p53-mediated suppression of HCC cell invasion. Taken together, our results showed how PAK4 overexpression in HCC promotes metastatic invasion by regulating p53 phosphorylation.postprin

Quinidine for Brugada syndrome: Panacea or poison?

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Increased serum levels and epithelial expression of macrophage migration inhibitory factor in gastric cancer

This journal suppl. contain abstracts of the 8th Medical Research Conference, Medical Science Group, Queen Mary Hospital, Hong Kongpublished_or_final_versio

Myocardial fiber length mapping with MR diffusion tensor imaging

Diffusion tensor MRI is emerging as a rapid, nondestructive method to map myocardial fiber organization. A precise biological description of myocardial fiber performance requires knowledge of four variables: length, force, velocity and time. However, study of quantification of myocardial fiber length is lacking. The current study aims to show myocardial fiber length maps of formalin-fixed heats. Diffusion tensor MRI with medium diffusion resolution (15 directions) was performed in one isolated pig heart. Fiber length maps were investigated in multiple short-axis slices. The results provide supplementary information of myocardial fiber organization. To our knowledge, the present study is the first report of the myocardial fiber length mapping. © 2005 IEEE.published_or_final_versio

Duration of dual antiplatelet therapy after drug-eluting stent implantation: Meta-analysis of large randomised controlled trials

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