Different protein tyrosine phosphatase superfamilies resulting from different gene reading frames

Protein tyrosine phosphatases (PTPs) are comprised of two superfamilies, the phosphatase I superfamily containing a single low-molecular-weight PTP (lmwPTP) family and the phosphatase II superfamily including both the higher-molecular-weight PTP (hmwPTP) and the dual-specificity phosphatase (DSP) families. The phosphatase I and H superfamilies are often considered to be the result of convergent evolution. The PTP sequence and structure analyses indicate that lmwPTPs, hmwPTPs, and DSPs share similar structures, functions, and a common signature motif, although they have low sequence identities and a different order of active sites in sequence or a circular permutation. The results of this work suggest that lmwPTPs and hmwPTPs/DSPs are remotely related in evolution. The earliest ancestral gene of PTPs could be from a short fragment containing about 90similar to120 nucleotides or 30similar to40 residues; however, a probable full PTP ancestral gene contained one transcript unit with two lmwPTP genes. All three PTP families may have resulted from a common ancestral gene by a series of duplications, fusions, and circular permutations. The circular permutation in PTPs is caused by a reading frame difference, which is similar to that in DNA methyltransferases. Nevertheless, the evolutionary mechanism of circular permutation in PTP genes seems to be more complicated than that in DNA methyltransferase genes. Both mechanisms in PTPs and DNA methyltransferases can be used to explain how some protein families and superfamilies came to be formed by circular permutations during molecular evolution.

Beyond theory: An examination of lean new product introduction practices in the UK

Interest is growing around the application of lean techniques to new product introduction (NPI). Although a relatively emergent topic compared with the application of 'lean' within the factory, since 2000 there has been an exponential rise in the literature on this subject. However, much of this work focuses on describing and extolling the virtues of the 'Toyota approach' to design. Therefore, by way of a stock take for the UK, the present authors' research has set out to understand how well lean product design practices have been adopted by leading manufacturers. This has been achieved by carrying out in-depth case studies with three carefully selected manufacturers of complex engineered products. This paper describes these studies, the detailed results and subsequent findings, and concludes that both the awareness and adoption of practices is generally embryonic and far removed from the theory advocated in the literature. © IMechE 2007.