The sequence of 5,037 amino acids composing the ryanodine receptor from rabbit skeletal muscle sarcoplasmic reticulum has been deduced by cloning and sequencing the complementary DNA. The predicted structure suggests that the calcium release channel activity resides in the C-terminal region of the receptor molecule, whereas the remaining portion constitutes the 'foot' structure spanning the junctional gap between the sarcoplasmic reticulum and the transverse tubule.

We have recently reported that angiotensin II (Ang II)-induced mitogen-activated protein kinase (MAPK) activation is mainly mediated by Ca 2؉ -dependent activation of a protein tyrosine kinase through G q -coupled Ang II type 1 receptor in cultured rat vascular smooth muscle cells (VSMC). In the present study, we found Ang II rapidly induced the tyrosine phosphorylation of the epidermal growth factor (EGF) receptor and its association with Shc and Grb2. These reactions were inhibited by the EGF receptor kinase inhibitor, AG1478. The Ang II-induced phosphorylation of the EGF receptor was mimicked by a Ca 2؉ ionophore and completely inhibited by an intracellular Ca 2؉ chelator. Thus, AG1478 abolished the MAPK activation induced by Ang II, a Ca 2؉ ionophore as well as EGF but not by a phorbol ester or platelet-derived growth factor-BB in the VSMC. Moreover, Ang II induced association of EGF receptor with catalytically active c-Src. This reaction was not affected by AG1478. These data indicate that Ang II induces Ca 2؉ -dependent transactivation of the EGF receptor which serves as a scaffold for pre-activated c-Src and for downstream adaptors, leading to MAPK activation in VSMC.

In cultured rat vascular smooth muscle cells, angiotensin II (Ang II) induced a rapid increase in mitogen-activated protein kinase (MAPK) activity through the Ang II type 1 receptor, which was insensitive to pertussis toxin but was abolished by the phospholipase C inhibitor, U73122. The Ang II-induced MAPK activation was not affected by the protein kinase C inhibitor, GF109203X, and was only partially impaired by pretreatment with a phorbol ester, whereas both treatments completely prevented MAPK activation by the phorbol ester. Intracellular Ca2+ chelation by TMB-8, but not extracellular Ca2+ chelation or inhibition of Ca2+ influx, abolished Ang II-induced MAPK activation. The calmodulin inhibitor, calmidazolium, and the tyrosine kinase inhibitor, genistein, completely blocked MAPK activation by Ang II as well as by the Ca2+ ionophore A23187. Ang II caused a rapid increase in the binding of GTP to p21(ras), and this was inhibited by genistein, TMB-8, and calmidazolium but not by pertussis toxin or GF109203X. These data suggest that Ang II-induced MAPK activation through the Ang II type 1 receptor could be mediated by p21(ras)activation through a currently unidentified tyrosine kinase that lies downstream of Gq-coupled Ca2+/calmodulin signals.

The source of the local tsunami of 17 th July 1998 that struck the north shore of Papua New Guinea remains controversial, and has been postulated as due either to seabed dislocation (fault) or sediment slump. Alternative source mechanisms of the tsunami were addressed by offshore investigation using. multibeam bathymetry, sub-bottom profiling, sediment sampling and observation from the JAMSTEC Dolphin 3K Remotely Operated Vehicle and Shinkai 2000 Manned Submersible. The area offshore of Sissano is a complex active convergent margin with subduction taking place along the New Guinea Trench. Dominant transpressional convergence results in diachronous collision of the highstanding North Bismarck Sea Plate in a westerly direction. The result is a morphological variation along the Inner Trench Slope, with the boundary between eastern and western segments located offshore Sissano in an area of on-and offshore subsidence. This subsidence, together with nearshore bathymetric focusing, is considered to increase the tsunamigenic potential of the Sissano area. The offshore data allow discrimination between tsunami generating mechanisms with the most probable source mechanism of the local tsunami as a sediment slump located offshore of Sissano Lagoon. The approximately 5-10 km 3 slump is located in an arcuate, amphitheatreshaped structure in cohesive sediments that failed through rotational faulting. In the area of the amphitheatre there is evidence of recent seabed movement in the form of fissures, brecciated angular sediment blocks, vertical slopes, talus deposits and active fluid expulsion that maintains a chemosynthetic vent fauna. Dating of the slump event may be approximated 2 by the age of the chemosynthetic faunas as well as by a seismic signal from the failing sediment mass. Faults in the area offshore Sissano are mainly dip-slip to the north with recent movement only along planes of limited lateral extent. A possible thrust fault is of limited extent and with minimal (cm) reverse movement. Further numerical modeling of the tsunami also supports the slump as source over fault displacements.

LRR-containing proteins are present in over 2000 proteins from viruses to eukaryotes. Most LRRs are 20-30 amino acids long, and the repeat number ranges from 2 to 42. The known structures of 14 LRR proteins, each containing 4-17 repeats, have revealed that the LRR domains fold into a horseshoe (or arc) shape with a parallel beta-sheet on the concave face and with various secondary structures, including alpha-helix, 3(10)-helix, and pII helix on the convex face. We developed simple methods to charactere quantitatively the arc shape of LRR and then applied them to all known LRR proteins. A quantity of 2Rsin(phi/2), in which R and phi are the radii of the LRR arc and the rotation angle about the central axis per repeating unit, respectively, is highly conserved in all the LRR proteins regardless of a large variety of repeat number and the radius of the LRR arc. The radii of the LRR arc with beta-alpha structural units are smaller than those with beta-3(10) or beta-pII units. The concave face of the LRR beta-sheet forms a surface analogous to a part of a Möbius strip.