Prospective of Ras signaling in stem cells

2008 ◽  
Vol 389 (7) ◽  
Author(s):  
Koushik Chakrabarty ◽  
Rolf Heumann
Keyword(s):  
Stem Cells ◽  
Biological Process ◽  
Large Family ◽  
Eukaryotic Cells ◽  
Signal Transduction Pathways ◽  
Ras Signaling ◽  
Intracellular Membrane ◽  
Predominant Role ◽  
Ras Signaling Pathway ◽  
Membrane Compartments

Abstract The Ras signaling pathway plays a predominant role during development and controls diverse biological process in all eukaryotic cells. It is a member of the large family of GTPases proteins that binds and hydrolyzes GTP. Ras is a lipid-anchored protein on the intracellular membrane compartments, and cycles between inactive GDP-bound and the signaling competent GTP-bound conformation. Studies have demonstrated Ras to be a central regulator in signal transduction pathways responding to diverse extracellular and intracellular stimuli. Much progress has been made towards delineating specific genes involved in the process of pluripotency and differentiation of stem cells. Here, we discuss recent aspects of Ras signaling pathways in mediating stem cell properties.

scholarly journals Probing the subcellular distribution of phosphatidylinositol reveals a surprising lack at the plasma membrane

2020 ◽  
Vol 219 (3) ◽  
Author(s):  
James P. Zewe ◽  
April M. Miller ◽  
Sahana Sangappa ◽  
Rachel C. Wills ◽  
Brady D. Goulden ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Subcellular Localization ◽  
Subcellular Distribution ◽  
Eukaryotic Cells ◽  
Intracellular Membrane ◽  
Membrane Function ◽  
Membrane Compartments ◽  
Health And Disease ◽  
Structural Lipid ◽  
And Function

The polyphosphoinositides (PPIn) are central regulatory lipids that direct membrane function in eukaryotic cells. Understanding how their synthesis is regulated is crucial to revealing these lipids’ role in health and disease. PPIn are derived from the major structural lipid, phosphatidylinositol (PI). However, although the distribution of most PPIn has been characterized, the subcellular localization of PI available for PPIn synthesis is not known. Here, we used several orthogonal approaches to map the subcellular distribution of PI, including localizing exogenous fluorescent PI, as well as detecting lipid conversion products of endogenous PI after acute chemogenetic activation of PI-specific phospholipase and 4-kinase. We report that PI is broadly distributed throughout intracellular membrane compartments. However, there is a surprising lack of PI in the plasma membrane compared with the PPIn. These experiments implicate regulation of PI supply to the plasma membrane, as opposed to regulation of PPIn-kinases, as crucial to the control of PPIn synthesis and function at the PM.

scholarly journals Probing the Subcellular Distribution of Phosphatidylinositol Reveals a Surprising Lack at the Plasma Membrane

2019 ◽  
Author(s):  
James P. Zewe ◽  
April Miller ◽  
Sahana Sangappa ◽  
Rachel C. Wills ◽  
Brady D. Goulden ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Subcellular Localization ◽  
Subcellular Distribution ◽  
Eukaryotic Cells ◽  
Intracellular Membrane ◽  
Membrane Function ◽  
Membrane Compartments ◽  
Health And Disease ◽  
Structural Lipid ◽  
And Function

AbstractThe polyphosphoinositides (PPIn) are central regulatory lipids that direct membrane function in eukaryotic cells. Understanding how their synthesis is regulated is crucial to revealing these lipids’ role in health and disease. PPIn are derived from the major structural lipid, phosphatidylinositol (PI). However, although the distribution of most PPIn have been characterized, the subcellular localization of PI available for PPIn synthesis is not known. Here, we have used several orthogonal approaches to map the subcellular distribution of PI, including localizing exogenous fluorescent PI, as well as detecting lipid conversion products of endogenous PI after acute chemogenetic activation of PI-specific phospholipase and 4-kinase. We report that PI is broadly distributed throughout intracellular membrane compartments. However, there is a surprising lack of PI in the plasma membrane compared to the PPIn. These experiments implicate regulation of PI supply to the plasma membrane, as opposed to regulation of PPIn-kinases, as crucial to the control of PPIn synthesis and function at the PM.SummaryZewe et al develop approaches to map the subcellular distribution of the major phospholipid, phosphatidylinositol (PI), revealing that the lipid is present in most membranes except for plasma membrane, where it is mainly found as PI4P and PI(4,5)P2.

scholarly journals Identification of the functional components of the Ras signaling pathway regulating pituitary cell-specific gene expression.

1994 ◽  
Vol 14 (3) ◽  
pp. 1553-1565 ◽  
Author(s):  
K E Conrad ◽  
J M Oberwetter ◽  
R Vaillancourt ◽  
G L Johnson ◽  
A Gutierrez-Hartmann
Keyword(s):  
Gene Expression ◽  
Pituitary Cell ◽  
Mitogen Activated Protein Kinase ◽  
Specific Gene ◽  
Ras Signaling ◽  
Raf Kinase ◽  
Prolactin Gene ◽  
Ras Signaling Pathway ◽  
Mitogen Activated Protein ◽  
Prolactin Promoter

Ras, a small GTP-binding protein, is required for functional receptor tyrosine kinase signaling. Ultimately, Ras alters the activity of specific nuclear transcription factors and regulates novel patterns of gene expression. Using a rat prolactin promoter construct in transient transfection experiments, we show that both oncogenic Ras and activated forms of Raf-1 kinase selectively stimulated the cellular rat prolactin promoter in GH4 rat pituitary cells. We also show that the Ras signal is completely blocked by an expression vector encoding a dominant-negative Raf kinase. Additionally, using a molecular genetic approach, we determined that inhibitory forms of p42 mitogen-activated protein kinase and an Ets-2 transcription factor interfere with both the Ras and the Raf activation of the rat prolactin promoter. These findings define a functional requirement for these signaling constituents in the activation of the prolactin gene, a cell-specific gene which marks the lactotroph pituitary cell type. Further, this analysis allowed us to order the components in the Ras signaling pathway as it impinges on regulation of prolactin gene transcription as Ras-->Raf kinase-->mitogen-activated protein kinase-->Ets. In contrast, we show that intact c-Jun expression inhibited the Ras-induced activation of the prolactin promoter, defining it as a negative regulator of this pathway, whereas c-Jun was able to enhance the Ras activation of an AP-1-driven promoter in GH4 cells. These data show that c-Jun is not the nuclear mediator of the Ras signal for the highly specialized, pituitary cell-specific prolactin cellular promoter. Thus, we have defined a model system which provides an ideal paradigm for studying Ras/Raf signaling pathways and their effects on neuroendocrine cell-specific gene regulation.

The Ras signaling pathway in Drosophila

1995 ◽  
Vol 5 (1) ◽  
pp. 44-50 ◽  
Author(s):  
David A. Wassarman ◽  
Marc Therrien ◽  
Gerald M. Rubin
Keyword(s):  
Signaling Pathway ◽  
Ras Signaling ◽  
Ras Signaling Pathway

scholarly journals Post-transcriptional gene regulation by the RNA binding protein IGF2BP3 is critical for MLL-AF4 mediated leukemogenesis

2020 ◽  
Author(s):  
Tiffany M Tran ◽  
Julia Philipp ◽  
Jaspal Bassi ◽  
Neha Nibber ◽  
Jolene Draper ◽  
...  
Keyword(s):  
Rna Binding ◽  
Leukemia Cell ◽  
Cellular Level ◽  
Ras Signaling ◽  
Therapeutic Approaches ◽  
Mrna Targets ◽  
Ras Signaling Pathway ◽  
Stem And Progenitor Cells ◽  
Transcriptional Gene Regulation ◽  
Poor Outcomes

ABSTRACTDespite recent advances in therapeutic approaches, patients with MLL-rearranged leukemia still have poor outcomes and a high risk of relapse. Here, we found that MLL-AF4, the most common MLL fusion protein in patients, transcriptionally induces IGF2BP3 and that IGF2BP3 strongly amplifies MLL-Af4 mediated leukemogenesis. Deletion of Igf2bp3 significantly increases the survival of mice with MLL-Af4 driven leukemia and greatly attenuates disease. At the cellular level, MLL-Af4 leukemia-initiating cells require Igf2bp3 for their function in leukemogenesis. eCLIP and transcriptome analysis of MLL-Af4 transformed stem and progenitor cells and MLL-Af4 bulk leukemia cells reveals a complex IGF2BP3-regulated post-transcriptional operon governing leukemia cell survival and proliferation. Critical mRNA targets include important leukemogenic genes such as in the Hoxa locus and numerous genes within the Ras signaling pathway. Together, our findings show that IGF2BP3 is an essential positive regulator of MLL-AF4 mediated leukemogenesis and is a potential therapeutic target in this disease.

scholarly journals Nogo-B receptor-mediated Ras signaling pathway is a target for suppressing proliferating hemangioma

JCI Insight ◽  
2021 ◽  
Author(s):  
Wenquan Hu ◽  
Zhong Liu ◽  
Valerie Salato ◽  
Paula E. North ◽  
Joyce Bischoff ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Ras Signaling ◽  
Ras Signaling Pathway

The effect of aquaporin 5 overexpression on the Ras signaling pathway

2008 ◽  
Vol 367 (2) ◽  
pp. 291-298 ◽  
Author(s):  
Janghee Woo ◽  
Juna Lee ◽  
Myoung Sook Kim ◽  
Se Jin Jang ◽  
David Sidransky ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Ras Signaling ◽  
Aquaporin 5 ◽  
Ras Signaling Pathway
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