Identification of p130(cas) as a substrate for the cytosolic protein tyrosine phosphatase PTP-PEST

PTP-PEST is a ubiquitously expressed, cytosolic, mammalian protein tyrosine phosphatase (PTP) which exhibits high specific activity in vitro, We have investigated the substrate specificity of PTP-PEST by a novel substrate-trapping approach in combination within vitro dephosphorylation experiments. We initially identified a prominent 130-kDa tyrosine-phosphorylated protein in pervanadate-treated HeLa cell lysates which was preferentially dephosphorylated by PTP-PEST in vitro, In order to identify this potential substrate, mutant (substrate-trapping) forms of PTP-PEST were generated which lack catalytic activity but retain the ability to bind substrates. These mutant proteins associated in stable complex-es exclusively with the same 130-kDa protein, which was identified as p130(cas) by immunoblotting. This exclusive association was observed in lysates from several cell lines and in transfected COS cells, but was not observed with other members of the PTP family, strongly suggesting that p130(cas) represents a major physiologically relevant substrate for PTP-PEST. Our studies suggest potential roles for PTP-PEST in regulation of p130(cas) function, These functions include mitogen- and cell adhesion-induced signalling events and probable roles in transformation by various oncogenes. These results provide the first demonstration of a PTP having an inherently restricted substrate a specificity in vitro and in vivo. The methods used to identify p130(cas) as a specific substrate for PTP-PEST are potentially applicable to any PTP and should therefore prove useful in determining the physiological substrates of other members of the PTP family

London governance and the politics of neighbourhood planning: a case for investigation

The Localism Act 2011 has successfully devolved planning powers to over 2,500 English communities, involving 14 million people, with over 700 ‘made’ neighbourhood plans legitimised by referendum. In London, however, there are less than one-tenth of the made plans than in the rest of England. Institutional resistance and policy choices may be implicated. Two national studies of neighbourhood planning are reviewed. The role of the local authority is found to be a crucial factor in determining progress, and issues of social deprivation and unequal access are highlighted. Theorisation is considered by reference to a range of academic studies of localism and neighbourhood planning. Distinctions made between ‘representative’ and ‘community’ localism, and objections to anti-political effects, are noted. There has been remarkably little research into borough governance and neighbourhood planning in the capital. Based upon evidence of anomalous and differentiated governance practice, a study in London is called for

‘If independence goes, the planning system goes’: New Political Governance and the English Planning Inspectorate

Radical restructuring of 'arms-length' government bodies following the 2010 UK national election signalled a change in relations between government and the civil service. This was seen as a major shift in modes of governance from 'new public management' to a more politicised mode of 'new political governance'. This paper presents an analysis of the impacts of these shifts on the English Planning Inspectorate, an executive agency central to the land-use planning system. It identifies measures by ministers to increase control over the Inspectorate that represent a shift in governance culture and a shift in the planning system itself

Neuropeptide Y concentrations in cerebrospinal fluid are unchanged in obesity

Neuropeptide Y (NPy) is a potent centrally acting appetite-stimulating peptide implicated in the regulation of energy balance. It induces hyperphagia and obesity when injected into the rat hypothalamus. Hypothalamic NPY and NPY mRNA levels are increased in spontaneously obese rats, suggesting that it may be involved in causing obesity in rodents. It is not known whether NPY has a role in the pathogenesis of obesity in man. NPY is found in human cerebrospinal fluid (CSF) and we have therefore compared CSF NPY levels in normal obese and non-obese individuals to determine whether NPY concentrations might be increased in obesity. We studied 25 clinically normal subjects (age 67 ± 5 years. male 11. female 14) undergoing spinal anaesthesia. None had any significant illness. Samples of 1 ml were freeze-dried and reconstituted to 100 ul and 35ul aliquots were assayed for NPY using an in-house RIA. CSF NPY levels were not correlated with body mass index (BMI) (r=O.088. p=O.673) and there were no differences in NPY concentrations between groups of subjects stratified for BMI: BMI 25 (n=ll), 702 ± 55 fmol/ml (differences between all groups. p>0l). CSF NPY levels are therefore not increased in human obesity. NPY is found in many brain regions outside the hypothalamic appetite-regulating nuclei, which could contribute to CSF levels. This negative observation does not therefore exclude a role of the peptide, acting specifically in the hypothalamus, in contributing to human obesity

Symmetry breaking in crossed magnetic and electric fields

We present the first observations of cylindrical symmetry breaking in highly excited diamagnetic hydrogen with a small crossed electric field, and we give a semiclassical interpretation of this effect. As the small perpendicular electric field is added, the recurrence strengths of closed orbits decrease smoothly to a minimum, and revive again. This phenomenon, caused by interference among the electron waves that return to the nucleus, can be computed from the azimuthal dependence of the classical closed orbits.Comment: 4 page REVTeX file including 5 postscript files (using psfig) Accepted for publication in Physical Review Letters. Difference from earlier preprint: we have discovered the cause of the earlier apparent discrepancy between experiment and theory and now achieve excellent agreemen

Transitions/relaxations in polyester adhesive/PET system

The correlations between the transitions and the dielectric relaxation processes of the oriented poly(ethylene terephthalate) (PET) pre-impregnated of the polyester thermoplastic adhesive have been investigated by differential scanning calorimetry (DSC) and dynamic dielectric spectroscopy (DDS). The thermoplastic polyester adhesive and the oriented PET films have been studied as reference samples. This study evidences that the adhesive chain segments is responsible for the physical structure evolution in the PET-oriented film. The transitions and dielectric relaxation modes’ evolutions in the glass transition region appear characteristic of the interphase between adhesive and PET film, which is discussed in terms of molecular mobility. The storage at room temperature of the adhesive tape involves the heterogeneity of the physical structure, characterized by glass transition dissociation. Thus, the correlation between the transitions and the dielectric relaxation processes evidences a segregation of the amorphous phases. Therefore, the physical structure and the properties of the material have been linked to the chemical characteristics