Signal transduction

About: Signal transduction is a research topic. Over the lifetime, 122628 publications have been published within this topic receiving 8209258 citations. The topic is also known as: GO:0007165.

Showing your ID: intrinsic disorder as an ID for recognition, regulation and cell signaling.

Abstract: Regulation, recognition and cell signaling involve the coordinated actions of many players. To achieve this coordination, each participant must have a valid identification (ID) that is easily recognized by the others. For proteins, these IDs are often within intrinsically disordered (also ID) regions. The functions of a set of well-characterized ID regions from a diversity of proteins are presented herein to support this view. These examples include both more recently described signaling proteins, such as p53, alpha-synuclein, HMGA, the Rieske protein, estrogen receptor alpha, chaperones, GCN4, Arf, Hdm2, FlgM, measles virus nucleoprotein, RNase E, glycogen synthase kinase 3beta, p21(Waf1/Cip1/Sdi1), caldesmon, calmodulin, BRCA1 and several other intriguing proteins, as well as historical prototypes for signaling, regulation, control and molecular recognition, such as the lac repressor, the voltage gated potassium channel, RNA polymerase and the S15 peptide associating with the RNA polymerase S-protein. The frequent occurrence and the common use of ID regions in important protein functions raise the possibility that the relationship between amino acid sequence, disordered ensemble and function might be the dominant paradigm for the molecular recognition that serves as the basis for signaling and regulation by protein molecules.

CD45: A Critical Regulator of Signaling Thresholds in Immune Cells

Abstract: Regulation of tyrosine phosphorylation is a critical control point for integration of environmental signals into cellular responses. This regulation is mediated by the reciprocal actions of protein tyrosine kinases and phosphatases. CD45, the first and prototypic receptor-like protein tyrosine phosphatase, is expressed on all nucleated hematopoietic cells and plays a central role in this process. Studies of CD45 mutant cell lines, CD45-deficient mice, and CD45-deficient humans initially demonstrated the essential role of CD45 in antigen receptor signal transduction and lymphocyte development. It is now known that CD45 also modulates signals emanating from integrin and cytokine receptors. Recent work has focused on regulation of CD45 expression and alternative splicing, isoform-specific differences in signal transduction, and regulation of phosphatase activity. From these studies, a model is emerging in which CD45 affects cellular responses by controlling the relative threshold of sensitivity to external stimuli. Perturbation of this function may contribute to autoimmunity, immunodeficiency, and malignancy. Moreover, recent advances suggest that modulation of CD45 function can have therapeutic benefit in many disease states.

IL-22 Inhibits Epidermal Differentiation and Induces Proinflammatory Gene Expression and Migration of Human Keratinocytes

Abstract: IL-22 belongs to a family of cytokines structurally related to IL-10, including IL-19, IL-20, IL-24, and IL-26 In contrast to IL-10, IL-22 has proinflammatory activities IL-22 signals through a class II cytokine receptor composed of an IL-22-binding chain, IL-22RA1, and the IL-10RB subunit, which is shared with the IL-10R In the present study, we show that short-term cultured human epidermal keratinocytes express a functional IL-22R but no IL-10R Accordingly, IL-22 but not IL-10 induces STAT3 activation in keratinocytes Using a cDNA array screening approach, real-time RT-PCR, and Western blot analysis, we demonstrate that IL-22 up-regulates, in a dose-dependent manner, the expression of S100A7, S100A8, S100A9, a group of proinflammatory molecules belonging to the S100 family of calcium-binding proteins, as well as the matrix metalloproteinase 3, the platelet-derived growth factor A, and the CXCL5 chemokine In addition, IL-22 induces keratinocyte migration in an in vitro injury model and down-regulates the expression of at least seven genes associated with keratinocyte differentiation Finally, we show that IL-22 strongly induces hyperplasia of reconstituted human epidermis Taken together, these results suggest that IL-22 plays an important role in skin inflammatory processes and wound healing