Akt and Pancreatic b-Cell Growth and Function

Ernesto Bernal-Mizrachi

The serine-threonine kinase Akt also known as protein kinase B is one of the most studied molecules. In addition to the important role in carcinogenesis, Akt is a major regulator of carbohydrate metabolism. Akt mediates insulin-dependent glucose uptake in insulin-sensitive tissues. Recent evidence u...

Biological Roles of Prion Domains

Sergey G. Inge-Vechtomov, Galina A. Zhouravleva and Yury O. Chernoff

In vivo amyloid formation is a widespread phenomenon in eukaryotes. Self-perpetuating amyloids provide a basis for the infectious or heritable protein isoforms (prions). At least for some proteins, amyloid-forming potential is conserved in evolution despite divergence of the amino acid (aa) se...

Cellular Signaling by Collagen-Binding Integrins

Jyrki Heino

Collagens are structural proteins of extracellular matrix that typically have triple helical domains of variable length.1 Collagens form, for example, the large fibers of connec tive tissues and networks in basement membranes, while some collagens are transmembrane proteins. Metazoans fr...

Chromatin and the Control of Hox Gene Expression

Antero-posterior patterning of the animal embryo is governed in part by the highly conserved Hox genes. In most animals studied to date, Hox genes are assembled within one or more clusters. The thirty-nine Hox genes of mice and humans are organized into four clusters, each located on a different chr...

Collagen-Binding Integrins and Disease

Beate Eckes, Bernhard Nieswandt and Thomas Krieg

Among the b1 family of integrin receptors there are 4 receptors that mediate bind ing to different collagens. These are a1a, a2b, a

Evolution of Integrin I-Domains

Mark S. Johnson and Danny Tuckwell

In humans, I domains are ~200 residue long sequences that are “inserted” into the N-terminal domain of all 8 integrin a subunits and 9 of the 18 integrin b subunits. The integrin I-domains are related to the von Willebrand factor A do...

Food and Milk Allergies

Mary H. Perdue and Martine Heyman

Oral tolerance is the usual response to antigens encountered via the gut mucosal immune system. However in some individuals, ingestion of food antigens does not result in a down-regulated system, but rather an immunologically-mediated allergic reaction. Such reactions occur in ~2-5% of the popula...

Function of a2b1 Integrin

Mary M. Zutter and Samuel A. Santoro

The a2b1 integrin serves as an extracellular matrix receptor for collagen and /or laminin, as well as several other nonmatrix ligands.1-3 Interactions between the a2b1 integrin and...

Integrin a1b1

Humphrey Gardner

Introduction The integrin a1 subunit was first discovered by Hemler et al as the a component of the Very Late Antigen I (VLA1) expressed on a subset of T cells in the joints of patients with rheumatoid arthritis,1 as well as in a s...

Integrin aEb7: Molecular Features and Functional Significance in the Immune System

Peter J. Kilshaw and Jonathan M.G. Higgins

Abstract Alpha E beta 7 is an a-I domain-containing integrin that is expressed mainly on T cells, dendritic cells and mast cells in mucosal tissues. Expression depends largely or solely on TGF-b. The best characterized ligand for

Integrin Recognition Motifs in Collagens

Richard W. Farndale

The vertebrate integrins are a family of twenty four heterodimeric transmembrane sig nalling and adhesion molecules, found in very many cells types where their expression and affinity is carefully regulated, reviewed in Chapter 1 and.1,2 Integrins mediate either cell–cell interactions, o...

Integrins in Immune and Inflammatory Disease

Antonin R. de Fougerolles

The adhesive interactions of cells with other cells and with extracellular matrix have a central role in regulating immune and inflammatory responses. Integrins are capable of acting at different points along the inflammatory cascade. They are important in initiation of immune responses,...

Macrophage – Leishmania Interactions: Complexities and Uncertainties from the Study of Leishmaniasis in Vivo

Paul M. Kaye

Leishmania parasites are intracellular pathogens residing predominantly within mono-nuclear phagocytes. Whilst valuable insights into the host-pathogen interaction have been obtained from the study of “typical” macrophage and dendritic cell populations in vitro, such studies may greatly underestimat...

Oxidative Damage and Repair in the Mitochondrial Genome

Lene Juel Rasmussen and Keshav K. Singh

DNA is constantly exposed to damaging agents from both endogenous and exogenous sources. If this damage is not repaired, it can lead to mutations and result in cellular dysfunction, including uncontrolled cell proliferation. Thus, in order to maintain the integrity of the genome, a complex net...

Paramyxovirus Entry

Katharine N. Bossart and Christopher C. Broder

The family Paramyxoviridae consists of a group of large, enveloped, negative-sense, single-stranded RNA viruses and contains many important human and animal pathogens. Molecular and biochemical characterization over the past decade has revealed an extraordinary breadth of biological diversity ...

Physiology of Somatostatin

Marek Pawlikowski

Somatostatin (SST) was originally discovered as a hypothalamic peptide which inhibits growth hormone (GH) secretion from the pituitary gland. It appears in two molecular forms, composed from 14 or 28 amino-acid residues. Moreover, another family of peptides, called cortistatins (CST), was desc...

Preformed Cell Structure and Cell Heredity

Janine Beisson

This chapter will first recall the phenomena of “cortical inheritance” observed and genetically demonstrated in Paramecium 40 years ago, and later in other ciliates (Tetrahymena, Oxytricha, Paraurostyla), and will analyze the deduced concept of “cytotaxis” or “structural memory”. The significa...

Reovirus Receptors, Cell Entry, and Proapoptotic Signaling

Pranav Danthi, Geoffrey H. Holm, Thilo Stehle and Terence S. Dermody

Mammalian orthoreoviruses (reoviruses) are members of the Reoviridae family of viruses. Reoviruses contain 10 double-stranded (ds) RNA gene segments enclosed in two concentric protein shells, called outer capsid and core. These viruses serve as a versatile experimental system for studies of vi...

Somatostatin Analogs: Lessons in Functional Complexity and Receptor Interactions

Michael D. Culler

Somatostatin (SST) was originally isolated from the hypothalamus as the key suppressor GH secretion, but is now known to be widely distributed throughout the body and to be involved in numerous physiological functions. While the varied activity of SST creates opportunities for its use as a the...

Somatostatin Analogs—New Perspectives

Gabriela Melen-Mucha and Marek Pawlikowski

Acromegaly and so-called neuroendocrine tumors (carcinoids, pancreatic endocrine tumors) are at present the only routine indications for somatostatin (SST) analogs therapy. However, the progress in the studies on somatostatin receptors (sst) and the development of the numerous new SST analog...

Somatostatin Receptors in Human Tumors: In Vitro Studies

Marek Pawlikowski

Neoplastic cells express and often even over-express the somatostatin receptors. It is important because the presence of sst receptors predicts—to some extent—the possibility of treatment with SST analogs. The presence of sst receptors may be examined in vivo, by means of the receptor scinti...

Somatostatin Receptors: Distribution in Normal Tissues and Transduction Mechanisms

Gabriela Melen-Mucha and Slawomir Mucha

receptors belonging to the family of G protein coupled receptors. So far five SST receptor subtypes (sst1-5) have been cloned and characterized. The genes for these receptor subtypes are localized on different chromosomes and are intronless, with one exception concerning sst2, which exists in tw...

Structural Aspects of Integrins

Robert C. Liddington

Structural studies on integrins have recently made great strides. In the past three years, crystal structures of the complete extracellular fragment of one integrin, aVb3,1 two a-I domains in complex with li...

Structure and Activation of b₂ - Integrins

Carl G. Gahmberg and Susanna Fagerholm

Cellular adhesion is essential for several leukocyte functions. A number of adhesion molecules are involved in various adhesive events, but perhaps the most important are the leukocyte specific b2-integrins (CD11/CD18). Recent work has explored integrin structu...

Structure and Function of a11b1

Donald Gullberg, Svetlana N. Popova and Carl-Fredrik Tiger

The a11 integrin chain constitutes the latest addition to the integrin family. a11b1 was originally identified on cultured human muscle cells, but recent studies have shown that it is not expressed on muscle...