Members of the fatty acid binding protein family are differentiation factors for the mammary gland

Mammary gland development is controlled by systemic hormones and by growth factors that might complement or mediate hormonal action. Peptides that locally signal growth cessation and stimulate differentiation of the developing epithelium have not been described. Here, we report that recombinant and wild-type forms of mammary-derived growth inhibitor (MDGI) and heart-fatty acid binding protein (FABP), which belong to the FABP family, specifically inhibit growth of normal mouse mammary epithelial cells (MEC), while growth of stromal cells is not suppressed. In mammary gland organ culture, inhibition of ductal growth is associated with the appearance of bulbous alveolar end buds and formation of fully developed lobuloalveolar structures. In parallel, MDGI stimulates its own expression and promotes milk protein synthesis. Selective inhibition of endogenous MDGI expression in MEC by antisense phosphorothioate oligonucleotides suppresses appearance of alveolar end buds and lowers the beta-casein level in organ cultures. Furthermore, MDGI suppresses the mitogenic effects of epidermal growth factor, and epidermal growth factor antagonizes the activities of MDGI. Finally, the regulatory properties of MDGI can be fully mimicked by an 11-amino acid sequence, represented in the COOH terminus of MDGI and a subfamily of structurally related FABPs. This peptide does not bind fatty acids. To our knowledge, this is the first report about a growth inhibitor promoting mammary gland differentiation

States and the political economy of unfree labour

A growing body of academic and policy research seeks to understand and address the problem of contemporary unfree labour. In this article, we argue that this literature could be strengthened by a stronger conceptualization of, and more systematic attention towards, the role of national states. In particular, we argue that there is a need to move beyond simplistic conceptualisations of states as simple agents of regulation and criminal justice enforcement who respond to the problem of unfree labour, and to recognize the causal and multifaceted role that national states play in creating the conditions in which unfree labour can flourish. We propose a framework to understand and compare the ways in which national states shape the political economy of unfree labour. Focusing on the United States, we outline three arenas of governance in which national states have been particularly central to enabling the conditions for unfree labour: the regulation of labour mobility, labour market regulation, and business regulation. We conclude by reflecting on the comparative political economy research that will be required to understand the role of different states in shaping the conditions in which unfree labour thrives or is eliminated

Migration Industries and the State: Guestwork Programs in East Asia

Studies of migration industries have demonstrated the critical role that border-spanning businesses play in international mobility. To date, most research has focused on meso-level entrepreneurial initiatives that operate in a legal gray area under a state that provides an environment for their growth or decline. Extending this work, the present article advances a taxonomy of the ways states partner with migration industries based on the nature of their relationship (formal or informal) and the type of actor involved (for-profit or non-profit). The analysis focuses on low-paid temporary migrant work programs — schemes that require substantial state involvement to function — and examines cases from the East Asian democracies with strong economies that have become net importers of migrants: Taiwan, Japan, and South Korea. The conclusion, incorporating cases beyond Asia, explicates the properties and limits of each arrangement based on the degree of formality and importance of profit

Fatty acid-binding protein from rat heart is phosphorylated on Tyr¹⁹ in response to insulin stimulation

The cytosolic fatty acid-binding protein from rat heart (H-FABP, M(r) 15,000) as well as FABP from mouse adipocytes (A-FABP, 62% homologous with H-FABP) contain a recognition sequence for protein tyrosine kinases, Asn-Phe-Asp-Asp-Tyr19. A-FABP has been shown by others to be partly phosphorylated on Tyr19, thus encouraging experiments designed to search for phosphotyrosine in H-FABP. For this purpose isolated cardiac myocytes were incubated with [32P]orthophosphate and analyzed by two-dimensional gel electrophoresis. A 15 kDa phosphoprotein present in the cytosolic protein fraction was specifically precipitated by a polyclonal antibody against rat heart FABP. Characterization of the phosphorylated FABP was facilitated by the development of an immunoaffinity purification procedure capable of isolating more than 200 micrograms FABP from four rat hearts in one step. Phosphoamino acid analysis and radiosequencing of the major tryptic phosphopeptide from immunopurified FABP revealed Tyr19 as the phosphorylated amino acid. Stimulation of cardiac myocytes with insulin in the presence of tyrosine phosphatase inhibitors led to a several-fold increase in the amount of phosphorylated FABP compared with a nearly undetectable level found without insulin stimulation, indicating that FABP may be a substrate for the insulin receptor tyrosine kinase. Phosphorylated FABP constitutes only a minor fraction compared to the large pool of FABP in the cardiac myocyte, thus obscuring the significance of this modification. However, as the phosphorylated Tyr19 residue is positioned within a helix-turn-helix-related domain of FABP, this modification may modulate a hitherto unknown DNA binding activity of FABP. A hypothesis is discussed in which phosphorylated FABP serves as a signalling molecule in the insulin signal transduction cascade