The second intracellular loop of the calcitonin gene-related peptide receptor provides molecular determinants for signal transduction and cell surface expression

The calcitonin gene-related peptide (CGRP) receptor is a heterodimer of a family B G-protein-coupled receptor, calcitonin receptor-like receptor (CLR), and the accessory protein receptor activity modifying protein 1. It couples to Gs, but it is not known which intracellular loops mediate this. We have identified the boundaries of this loop based on the relative position and length of the juxtamembrane transmembrane regions 3 and 4. The loop has been analyzed by systematic mutagenesis of all residues to alanine, measuring cAMP accumulation, CGRP affinity, and receptor expression. Unlike rhodopsin, ICL2 of the CGRP receptor plays a part in the conformational switch after agonist interaction. His-216 and Lys-227 were essential for a functional CGRP-induced cAMP response. The effect of (H216A)CLR is due to a disruption to the cell surface transport or surface stability of the mutant receptor. In contrast, (K227A)CLR had wild-type expression and agonist affinity, suggesting a direct disruption to the downstream signal transduction mechanism of the CGRP receptor. Modeling suggests that the loop undergoes a significant shift in position during receptor activation, exposing a potential G-protein binding pocket. Lys-227 changes position to point into the pocket, potentially allowing it to interact with bound G-proteins. His-216 occupies a position similar to that of Tyr-136 in bovine rhodopsin, part of the DRY motif of the latter receptor. This is the first comprehensive analysis of an entire intracellular loop within the calcitonin family of G-protein-coupled receptor. These data help to define the structural and functional characteristics of the CGRP-receptor and of family B G-protein-coupled receptors in general. © 2006 by The American Society for Biochemistry and Molecular Biology, Inc.

Facility closure management:the case of Vauxhall Motors Luton

Purpose – The purpose of the paper is to present the findings of a study of factory closure management. It details the sequence and the results of the key strategic manufacturing management decisions made from the time of the announcement of the plant closure to the cessation of operations. The paper also includes an analysis of the human resource management (HRM) actions taken during this same time period and their consequences upon all those involved in the closure management process. Design/methodology/approach – The case study methodology consisted of two initial site visits to monitor closure management effectiveness (adherence to plan and the types and frequency of closure management communications). During these visits, documentary evidence of the impact of the closure decision upon production performance was also collected (manufacturing output and quality performance data). Following plant closure, interviews were held with senior business, production and HRM managers and production personnel. A total of 12 interviews were carried out. Findings – The case study findings have informed the development of a conceptual model of facility closure management. Information obtained from the interviews suggests that the facility closure management process consists of five key management activities. The unexpected announcement of a factory closure can cause behavioural changes similar to those of bereavement, particularly by those employees who are its survivors. In addition, similar reactions to the closure announcement may be displayed by those who choose to remain employed by the factory owner throughout the phased closure of the plant. Originality/value – Facility closure management is an insufficiently researched strategic operations management activity. This paper details a recommended procedure for its management. A conceptual model has also been developed to illustrate the links between the key facility closure management tasks and the range of employee changes of behaviour that can be induced by their execution.

IT support for managing aircraft spares in a closed-loop supply chain

This paper reports on the development of elements of an e-supply chain management system for managing maintenance, repair and overhaul (MRO) relationships in the aerospace industry. A standard systems development methodology has been followed to produce a process model (i.e. the AMSCR model); an information model (i.e. business rules) and a computerised information management capability (i.e. automated optimisation). The proof of concept for this web-based MRO supply chain system has been established through the collaboration with a sample of the different types of supply chain members. The proven benefit is a reduction in the stock-holding costs for the whole supply chain whilst also minimising non-flying time of the aircraft that the supply chain supports. This type of system is now vital in an industry that has continuously decreasing profit margins, which in turn means pressure to reduce servicing times and increase the interval between maintenance actions.

Achieving closure through knowledge management strategy

Case studies of knowledge management practices are often conducted in organizations where the aim is to manage knowledge for future operational improvements. What about knowledge management for organizations with limited life-spans that are preparing for closure? Such organizations are not common but can benefit from knowledge management strategy. This case study concerns the knowledge management strategy of an organization that is preparing for its final phase of operations. We facilitated two group workshops with senior managers to scope a strategy, following which the organization initiated a set of projects to implement the resulting actions. This paper reviews their implemented actions against those designed in the workshop to shed light on knowledge management in this uncommon situation.