Plasma membrane nanoswitches generate high-fidelity Ras signal transduction

2007 ◽  
Vol 9 (8) ◽  
pp. 905-914 ◽  
Author(s):  
Tianhai Tian ◽  
Angus Harding ◽  
Kerry Inder ◽  
Sarah Plowman ◽  
Robert G. Parton ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Plasma Membrane ◽  
High Fidelity ◽  
Ras Signal Transduction

scholarly journals Ras plasma membrane signalling platforms

2005 ◽  
Vol 389 (1) ◽  
pp. 1-11 ◽  
Author(s):  
John F. HANCOCK ◽  
Robert G. PARTON
Keyword(s):  
Signal Transduction ◽  
Plasma Membrane ◽  
Cell Signalling ◽  
Dynamic Structure ◽  
Signal Transduction Pathways ◽  
Ras Proteins ◽  
Complex Dynamic ◽  
Additional Level ◽  
Ras Signal Transduction

The plasma membrane is a complex, dynamic structure that provides platforms for the assembly of many signal transduction pathways. These platforms have the capacity to impose an additional level of regulation on cell signalling networks. In this review, we will consider specifically how Ras proteins interact with the plasma membrane. The focus will be on recent studies that provide novel spatial and dynamic insights into the micro-environments that different Ras proteins utilize for signal transduction. We will correlate these recent studies suggesting Ras proteins might operate within a heterogeneous plasma membrane with earlier biochemical work on Ras signal transduction.

Differential Expression of ras Signal Transduction Mediators in Verrucous and Squamous Cell Carcinomas of the Upper Aerodigestive Tract

2001 ◽  
Vol 125 (9) ◽  
pp. 1200-1203
Author(s):  
Julie L. Lessard ◽  
Robert A. Robinson ◽  
Henry T. Hoffman
Keyword(s):  
Signal Transduction ◽  
Squamous Cell ◽  
Gene Mutations ◽  
Squamous Cell Carcinomas ◽  
Aerodigestive Tract ◽  
Upper Aerodigestive Tract ◽  
Immunohistochemical Expression ◽  
Ras Gene ◽  
Extracellular Signal ◽  
Ras Signal Transduction

Abstract Context.—ras gene mutations and expression of its gene product have been described in verrucous and squamous cell carcinomas. Other downstream signal-transduction mediators, extracellular signal-regulated kinases 1 and 2 (ERK-1 and ERK-2) and Raf-1, have not yet been as extensively studied. Objective.—To determine patterns of expression of ERK-1, ERK-2, and Raf-1 in verrucous and squamous cell carcinomas of the upper aerodigestive tract. Design.—Seventeen verrucous carcinomas and 10 squamous cell carcinomas of the upper aerodigestive tract were examined for the immunohistochemical expression of ERK-1, ERK-2, and Raf-1 product. Results.—Raf-1 expression was intensely expressed in the most basal portions of the epithelium in verrucous carcinomas, but was minimally expressed in the suprabasalar areas. Anti-Raf-1 staining of the squamous cell carcinomas was diffuse and patchy throughout the tumor cells and was weak in intensity. There was no geographic preference of staining. The cytoplasmic expression of both ERK-1 and ERK-2 was predominantly negative in the most basal layers of the epithelium in the verrucous carcinomas, but was positive in the suprabasalar region of the epithelium. Immunohistochemical expression of ERK-1 and ERK-2 in the squamous carcinomas was diffuse throughout the tumor. Conclusion.—There is strong correlation of the geographic expression of these mediators of ras signal transduction in verrucous and squamous carcinomas, but the cause of these differences remains unclear at present. The expression of these mediator proteins may have potential for diagnosis, as well as in understanding the biologic behavior of these lesions.

scholarly journals Morphological Alterations of CAD Cells Overexpressing AKT1

2020 ◽  
Vol 26 (S2) ◽  
pp. 1354-1358
Author(s):  
James Wachira
Keyword(s):  
Signal Transduction ◽  
Plasma Membrane ◽  
Cell Survival ◽  
Fluorescent Protein ◽  
Morphological Changes ◽  
Protein Localization ◽  
Signal Transduction Pathways ◽  
Morphological Alterations ◽  
Cellular Models ◽  
Cad Cells

AbstractCAD cells are neuronal cells used in studies of cell differentiation and in cellular models of neuropathology. When cultured in differentiation medium, CAD cells exhibit characteristics of mature neurons including the generation of action potential. In addition to being a central signaling kinase in cell survival, AKT1 plays important roles in the nervous system including neuroplasticity and this study examined the localization of exogenous AKT1 in CAD cells. Neuropeptides modulate many signal transduction pathways and melacortins are implicated in regulating growth factor signal transduction pathways, including the PI3K/AKT pathway. AKT1-DsReD was transfected into CAD cells that were stably expressing melanocortin 3-receptor-GFP (MC3R-GFP), a G-protein coupled receptor. The cells were imaged with confocal microscopy to determine the fluorescent protein localization patterns. AKT1-DsRed was predominantly localized in the cytoplasm and the nucleus. Further, expression of exogenous AKT1 in these cell lines led to morphological changes reminiscent of apoptosis. As expected, MC3R-GFP localized to the plasma membrane but it internalized upon cell stimulation with the cognate ligand. In limited areas of the plasma membrane, AKT1-DsRed and MC3R-GFP were colocalized. In conclusion, quantitative studies to understand the role of relative levels of AKT1 in determining cell survival are needed.

scholarly journals Fluorescent, short-chain C6-NBD-sphingomyelin, but not C6-NBD-glucosylceramide, is subject to extensive degradation in the plasma membrane: implications for signal transduction related to cell differentiation

1995 ◽  
Vol 309 (3) ◽  
pp. 905-912 ◽  
Author(s):  
J W Kok ◽  
T Babia ◽  
K Klappe ◽  
D Hoekstra
Keyword(s):  
Signal Transduction ◽  
Plasma Membrane ◽  
Cell Differentiation ◽  
Plasma Membranes ◽  
Cell Types ◽  
Short Chain ◽  
Synthetic Activity ◽  
Intact Cells ◽  
Ht29 Cells ◽  
Extensive Degradation

The involvement of the plasma membrane in the metabolism of the sphingolipids sphingomyelin (SM) and glucosylceramide (GlcCer) was studied, employing fluorescent short-chain analogues of these lipids, 6-[N-(7-nitro-2,1,3-benzoxadiazol-4-yl) amino]hexanoylsphingosylphosphorylcholine (C6-NBD-SM), C6-NBD-GlcCer and their common biosynthetic precursor C6-NBD-ceramide (C6-NBD-Cer). Although these fluorescent short-chain analogues are metabolically active, some caution is to be taken in view of potential changes in biophysical/biochemical properties of the lipid compared with its natural counterpart. However, these short-chain analogues offer the advantage of studying the lipid metabolic enzymes in their natural environment, since detergent solubilization is not necessary for measuring their activity. These studies were carried out with several cell types, including two phenotypes (differing in state of differentiation) of HT29 cells. Degradation and biosynthesis of C6-NBD-SM and C6-NBD-GlcCer were determined in intact cells, in their isolated plasma membranes, and in plasma membranes isolated from rat liver tissue. C6-NBD-SM was found to be subject to extensive degradation in the plasma membrane, due to neutral sphingomyelinase (N-SMase) activity. The extent of C6-NBD-SM hydrolysis showed a general cell-type dependence and turned out to be dependent on the state of cell differentiation, as revealed for HT29 cells. In undifferentiated HT29 cells N-SMase activity was at least threefold higher than in its differentiated counterpart. In contrast, in all cell types studied, very little if any biosynthesis of C6-NBD-SM from the precursor C6-NBD-Cer occurred. Moreover, in the case of C6-NBD-GlcCer, neither hydrolytic nor synthetic activity was found to be associated with the plasma membrane. These results are discussed in the context of the involvement of the sphingolipids SM and GlcCer in signal transduction pathways in the plasma membrane.

Kinase-anchoring proteins in ciliary signal transduction

2021 ◽  
Vol 478 (8) ◽  
pp. 1617-1629
Author(s):  
Janani Gopalan ◽  
Linda Wordeman ◽  
John D. Scott
Keyword(s):  
Signal Transduction ◽  
Brownian Motion ◽  
Plasma Membrane ◽  
Primary Cilium ◽  
Regulatory Proteins ◽  
Macromolecular Complexes ◽  
Regulatory Enzymes ◽  
Ciliary Function ◽  
Anchoring Proteins ◽  
Signal Relay

Historically, the diffusion of chemical signals through the cell was thought to occur within a cytoplasmic soup bounded by the plasma membrane. This theory was predicated on the notion that all regulatory enzymes are soluble and moved with a Brownian motion. Although enzyme compartmentalization was initially rebuffed by biochemists as a ‘last refuge of a scoundrel', signal relay through macromolecular complexes is now accepted as a fundamental tenet of the burgeoning field of spatial biology. A-Kinase anchoring proteins (AKAPs) are prototypic enzyme-organizing elements that position clusters of regulatory proteins at defined subcellular locations. In parallel, the primary cilium has gained recognition as a subcellular mechanosensory organelle that amplifies second messenger signals pertaining to metazoan development. This article highlights advances in our understanding of AKAP signaling within the primary cilium and how defective ciliary function contributes to an increasing number of diseases known as ciliopathies.

ras Gene Mutations and Expression of Ras Signal Transduction Mediators in Gastric Adenocarcinomas

2002 ◽  
Vol 126 (9) ◽  
pp. 1096-1100 ◽  
Author(s):  
Jinyoung Yoo ◽  
Sonya Y. Park ◽  
Robert A. Robinson ◽  
Seok Jin Kang ◽  
Woong Shick Ahn ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Tertiary Care ◽  
Immunohistochemical Analysis ◽  
Intestinal Type ◽  
Ras Gene ◽  
Ras Mutations ◽  
Korean Patients ◽  
Gene Alteration ◽  
Gastric Adenocarcinomas ◽  
Ras Signal Transduction

Abstract Objective.—To investigate ras gene alteration in human gastric adenocarcinomas and its potential relationship to ras signal transduction mediators. Design.—Genomic DNA from 104 gastric tumors were analyzed by sequencing of polymerase chain reaction–amplified products for the presence of ras mutations. All the samples were further investigated with the use of immunohistochemical analysis for ERK1 and ERK2. Setting.—Tertiary care teaching hospital. Patients.—Seventy patients from a Korean population and 34 from a Midwestern US population composed of white Americans and African Americans. Results.—Fifteen tumors (14%) were positive for either H-ras or K-ras mutation: 9 (13%) of 70 Korean patients and 6 (18%) of 34 US patients. Seven (78%) of the 9 mutated tumors from Korean patients and all 6 (100%) from the US patients were intestinal-type lesions. Either ERK1 and/or ERK2 was overexpressed in 68 samples (65%). No association was established between ras mutations and overexpression of ERK1/2. However, the correlation between ERK1/2 and progression (early vs late) was statistically significant (P = .007). Conclusions.—These data suggest that ras mutations are uncommon in gastric adenocarcinomas and that differing racial and/or geographic mechanisms may not underlie ras gene alteration. Most ras mutations were, however, observed in the group of intestinal-type samples, supporting the different genetic mechanisms of carcinogenesis between the intestinal- and diffuse-type tumors. It is noteworthy that enhanced ERK1/2 activity could be one of the characteristics of tumor invasiveness in gastric cancers.

Mechanisms of Hormone Action

2011 ◽  
Author(s):  
Stephen R. Hammes ◽  
Carole R. Mendelson
Keyword(s):  
Signal Transduction ◽  
Plasma Membrane ◽  
Nuclear Receptors ◽  
Plasma Membranes ◽  
Hormone Receptors ◽  
Membrane Receptors ◽  
Endocrine Disorders ◽  
Messenger Rnas ◽  
Dihydroxyvitamin D3 ◽  
Transduction Mechanisms

The capacity of a cell to respond to a particular hormone depends on the presence of cellular receptors specific for that hormone. After binding hormone, the receptor is biochemically and structurally altered, resulting in its activation; the activated receptor then mediates all of the actions of the hormone on the cell. The steroid and thyroid hormones as well as retinoids and 1,25-dihydroxyvitamin D3 diffuse freely through the lipophilic plasma membrane of the cell and interact with receptors that are primarily within the nucleus. On activation, the receptors alter the transcription of specific genes, resulting in changes in the levels of specific messenger RNAs (mRNAs), which are in turn translated into proteins. Hormones that are water soluble, such as the peptide and polypeptide hormones, catecholamines, and other neurotransmitters, as well as the relatively hydrophobic prostaglandins, interact with receptors in the plasma membrane. After hormone binding, the activated membrane receptors initiate signal transduction cascades that result in changes in enzyme activities and alterations in gene expression. In this chapter, the properties of various classes of receptors that are localized within the plasma membranes of target cells and the signal transduction mechanisms that mediate interactions with their ligands will first be addressed. This will be followed by consideration of the structural properties of the nuclear hormone receptors, the events that result in their activation, and the mechanisms whereby the activated nuclear receptors alter the expression of specific genes. Finally, a number of endocrine disorders that are caused by alterations in the number and/or function of plasma membranes and nuclear receptors will be reviewed. The function of a receptor is to recognize a particular hormone among all the molecules in the environment of the cell at a given time and, after binding the hormone, to transmit a signal that ultimately results in a biological response. Hormones are normally present in the circulation in extremely low concentrations, ranging from 10 –9 to 10 –11 M.

Sign in / Sign up

Export Citation Format

Share Document