No evidence for expression of the insulin-regulatable glucose transporter in endothelial cells

A major effect of insulin is to increase glucose transport in muscle and fat. A family of genes encoding distinct mammalian glucose transporters has recently been elucidated. One of these, the insulin-regulatable glucose transporter (IRGT), is primarily expressed in muscle and fat, tissues that exhibit insulin-dependent glucose transport. Insulin promotes glucose transport in these tissues by stimulating movement of the glucose transporter from an intracellular location to the plasma membrane. Recent studies, however, suggest that an additional effect of insulin in these tissues may be the facilitation of glucose transport, presumably across capillary endothelium. This hypothesis is based on the localization of the IRGT in endothelial cells specific to muscle and adipose tissue. We report here, however, on morphological and biochemical studies using several different IRGT-specific antibodies in which we could not reproduce these results.     

I-J epitopes are adaptively acquired by T cells differentiated in the chimaeric condition

I-J has been defined as a locus mapped in the murine major histocompatibility complex (MHC) which encodes serological markers found primarily on the surface of suppressor T cells (TS) and soluble suppressor factors (TSF). Recent studies have, however, revealed that there is no such specialized locus within the MHC at the DNA level. As the existence of I-J determinants at the protein level on functional T cells, T-cell clones and hybridomas has been confirmed by several serological and biochemical studies, this contradiction has raised serious arguments in the immunological community concerning the nature, origin and expression of I-J determinants. We have raised a number of monoclonal antibodies against the polymorphic structure of I-J molecules, and have studied the expression of I-J epitopes on T cells derived from irradiated bone marrow chimaeras in which stem cells of different genotype differentiated into T cells under the foreign host MHC environment. The results, presented here, indicate that I-J epitopes are not primarily determined by the MHC genes of the stem cells themselves, but are adaptively acquired by T cells differentiated in the chimaeric condition according to the environmental MHC phenotype. Thus, the serologically detectable I-J epitopes are found to be associated with inducible T-cell receptors recognizing self class II MHC antigens.     

The response of cyclic 3',5'-AMP and cyclic 3',5'-GMP phosphodiesterases to experimental diabetes

Alloxan diabetes caused a decrease in cyclic AMP phosphodiesterase in all affected rat tissues. Cyclic GMP phosphodiesterase activity was, however, decreased in adipose and liver, but increased increased in heart and uterus.     

Regulation of a protein synthesis initiation factor by adenovirus virus-associated RNA

A small RNA accumulating late in adenovirus infection is required for efficient protein synthesis, although not specifically for the translation of viral proteins. This RNA maintains the activity of an initiation factor catalysing the earliest step of polypeptide chain initiation.     

A point mutation in the neu oncogene mimics ligand induction of receptor aggregation

The rat neu gene, which encodes a protein closely related to the epidermal growth factor receptor, is a proto-oncogene that can be converted into an oncogene by a point mutation. Both genes encode proteins with a relative molecular mass of 185,000 but the question of why the neu gene product, p185neu, is oncogenic, whereas the product of c-neu, p185c-neu, is not, remains unanswered. The proteins have several features common to the family of tyrosine kinase growth-factor receptors, including cysteine-rich external domains, a hydrophobic transmembrane region and a cytoplasmic tyrosine kinase domain. The oncogenic p185neu differs from p185c-neu by an amino-acid substitution in the transmembrane region of the glycoprotein: this replacement of valine by glutamic acid at position 664 induces increased intrinsic tyrosine kinase activity which is associated with transformation. Many glycoproteins with charged amino acids in the transmembrane region exist as multimeric complexes at the plasma membrane. We have therefore investigated the association state of both products of the neu gene and show that the oncoprotein p185neu is organized at the plasma membrane primarily in an aggregated form, but that p185c-neu is not. Induction of an aggregated state may mimic aspects of ligand-induced receptor aggregation resulting in enzymatic activation that leads to cellular transformation.