Mechanism and Physiological Significance of Growth Factor-Related Autophagy

Physiology ◽  
2013 ◽  
Vol 28 (6) ◽  
pp. 423-431 ◽  
Author(s):  
Terytty Yang Li ◽  
Shu-Yong Lin ◽  
Sheng-Cai Lin
Keyword(s):  
Growth Factors ◽  
Growth Factor ◽  
Cell Fate ◽  
Energy Homeostasis ◽  
Growth Factor Signaling ◽  
Cell Fate Determination ◽  
Natural Substances ◽  
Autophagy Induction ◽  
Cell Growth And Differentiation ◽  
Intracellular Energy

Growth factors, typically defined as natural substances capable of stimulating cell growth and differentiation, are vital regulators for the survival of metazoan cells. In this review, we will focus on growth factor signaling pathways that are closely related to autophagy induction and discuss the critical roles of this fascinating cellular process in intracellular energy homeostasis, cell fate determination, and pathophysiological regulation.

Abstract 168: Contribution of Vascular Endothelial Growth Factor Signaling to Fate Specification in Cardiomyocytes

2014 ◽  
Vol 115 (suppl_1) ◽  
Author(s):  
Taylor Y Lu ◽  
Courtney K Domigan ◽  
Vaspour Antanesian ◽  
Yasuhiro Nakashima ◽  
Atsushi Nakano ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Cell Fate ◽  
Heart Development ◽  
Embryonic Stem ◽  
Growth Factor Signaling ◽  
Vascular Endothelial ◽  
Rt Pcr ◽  
Cardiac Morphogenesis ◽  
Endothelial Growth Factor

Vascular endothelial growth factor (VEGF) is one of the pivotal proangiogenic growth factors that has long contributed to our knowledge of blood vessel and circulatory maintenance as well as angiogenesis in both pathology and pathophysiology. However, the non-canonical functions of VEGF in cardiac morphogenesis have not been well characterized. Here, we examined how VEGF regulates cardiomyocyte cell fate. Using chimeric embryos harboring both wild type and VEGF-null embryonic stem cells, we observed that derivatives of VEGF null cells were preferentially recruited to the atrium of the heart in comparison to the ventricles. To further provide physiologic context of this finding, we used reporter-LacZ staining and RT-PCR and found that endogenous VEGF was indeed expressed at much lower levels in the atrium but highly expressed in the ventricle early in cardiac morphogenesis. These data lead to our hypothesis that cell-autonomous expression of VEGF is a determinant of atrial vs. ventricular cardiomyocyte cell fate. To test this hypothesis, we used a VEGF knock-in mouse model of Sm22Cre x Rosa 26 VEGF. VEGF overexpression in cardiomyocytes (and smooth muscle) at E8.5 resulted in lethality by P1 and thickened atrial and ventricular walls in mutant embryos as characterized by histology (H&E, IF). We further explored the molecular changes underlying this phenotype via microarray and RT-PCR and find disruptions in molecular markers necessary for wall development, specifically: Notch-1, BMP10, Nrg-1. Taken together, our data indicates that aberrant embryonic VEGF signaling disrupts several critical signaling pathways and that overexpression leads to disruption of cardiomyocyte proliferation and cardiac morphogenesis. These findings add to the foundation of better understanding heart development, laying the groundwork for future therapy of congenital and acquired cardiac disease.

Basic FGF and TGF-beta 1 influence commitment to melanogenesis in neural crest-derived cells of avian embryos

Development ◽  
1991 ◽  
Vol 111 (2) ◽  
pp. 635-645 ◽  
Author(s):  
K.M. Stocker ◽  
L. Sherman ◽  
S. Rees ◽  
G. Ciment
Keyword(s):  
Growth Factors ◽  
Growth Factor ◽  
Neural Crest ◽  
Cell Fate ◽  
Transforming Growth Factor Beta ◽  
Culture Medium ◽  
Transforming Growth Factor ◽  
Neutralizing Antibody ◽  
Pigment Cells ◽  
Tgf Beta

In previous studies, we showed that neural crest (NC)-derived cells from embryonic quail dorsal root ganglia (DRG) and peripheral nerve (PN), which do not normally give rise to melanocytes, become committed to melanogenesis following treatment in culture with the phorbol ester drug 12-O-tetradecanoyl phorbol-13-acetate (TPA). These and other observations support the notion that melanocytes and Schwann cells are derived from a common bipotent intermediate in the neural crest lineage—the melanocyte/Schwann cell progenitor. In this study, we test the possibility that peptide growth factors found in the embryonic environment might act similarly to TPA to influence the fates of these cells. DRG and PN explants were cultured in medium supplemented with a variety of growth factors, and then the cultures were examined for the presence of pigment cells. We found that basic fibroblast growth factor (bFGF), but not various other growth factors, induced pigmentation in about 20% of these cultures. When low concentrations of TPA were included in the culture medium, bFGF augmented the TPA-induced pigmentation, significantly increasing the proportion of pigmented cultures. These effects of bFGF were age-dependent, and could be blocked by addition of a bFGF-neutralizing antibody to the culture medium. In contrast to these stimulatory effects of bFGF, transforming growth factor-beta 1 (TGF-beta 1) was found to inhibit the TPA- or bFGF-induced pigmentation of DRG cultures. These data suggest, therefore, that at least some NC-derived cells are responsive to bFGF and TGF-beta 1, and that these growth factors may play an important role in the control of NC cell fate.

scholarly journals AIB1 Is a Conduit for Kinase-Mediated Growth Factor Signaling to the Estrogen Receptor

2000 ◽  
Vol 20 (14) ◽  
pp. 5041-5047 ◽  
Author(s):  
Jaime Font de Mora ◽  
Myles Brown
Keyword(s):  
Estrogen Receptor ◽  
Growth Factors ◽  
Growth Factor ◽  
Mitogen Activated Protein Kinase ◽  
Growth Factor Signaling ◽  
Breast Cancers ◽  
Mapk Activation ◽  
Mitogen Activated Protein

ABSTRACT Growth factor modulation of estrogen receptor (ER) activity plays an important role in both normal estrogen physiology and the pathogenesis of breast cancer. Growth factors are known to stimulate the ligand-independent activity of ER through the activation of mitogen-activated protein kinase (MAPK) and the direct phosphorylation of ER. We found that the transcriptional activity of AIB1, a ligand-dependent ER coactivator and a gene amplified preferentially in ER-positive breast cancers, is enhanced by MAPK phosphorylation. We demonstrate that AIB1 is a phosphoprotein in vivo and can be phosphorylated in vitro by MAPK. Finally, we observed that MAPK activation of AIB1 stimulates the recruitment of p300 and associated histone acetyltransferase activity. These results suggest that the ability of growth factors to modulate estrogen action may be mediated through MAPK activation of the nuclear receptor coactivator AIB1.

scholarly journals Fibroblast Growth Factor Signaling during Early Vertebrate Development

2004 ◽  
Vol 26 (1) ◽  
pp. 63-77 ◽  
Author(s):  
Ralph T. Böttcher ◽  
Christof Niehrs
Keyword(s):  
Growth Factors ◽  
Growth Factor ◽  
Fibroblast Growth Factors ◽  
Growth Factor Signaling ◽  
Fibroblast Growth ◽  
Vertebrate Development ◽  
Fgf Signaling ◽  
Fibroblast Growth Factor Signaling ◽  
Cellular Processes ◽  
Differentiation And Proliferation

Fibroblast growth factors (FGFs) have been implicated in diverse cellular processes including apoptosis, cell survival, chemotaxis, cell adhesion, migration, differentiation, and proliferation. This review presents our current understanding on the roles of FGF signaling, the pathways employed, and its regulation. We focus on FGF signaling during early embryonic processes in vertebrates, such as induction and patterning of the three germ layers as well as its function in the control of morphogenetic movements.

scholarly journals A Fyn - specific biosensor reveals localized, pulsatile kinase activity and spatially regulated signaling crosstalk

2019 ◽  
Author(s):  
Ananya Mukherjee ◽  
Randhir Singh ◽  
Sreeram Udayan ◽  
Sayan Biswas ◽  
Purushotham Pothula ◽  
...  
Keyword(s):  
Growth Factor ◽  
Cell Fate ◽  
Kinase Activity ◽  
Activity Patterns ◽  
Live Cells ◽  
Structural Basis ◽  
Cell Physiology ◽  
Growth Factor Signaling ◽  
Protein Activity ◽  
Signaling Crosstalk

AbstractCell behavior is controlled through spatio-temporally localized protein activity. Despite unique and often contradictory roles played by Src-family-kinases (SFKs) in regulating cell physiology, activity patterns of individual SFKs have remained elusive. Here, we report a biosensor for specifically visualizing active conformation of SFK-Fyn in live cells. We deployed combinatorial library screening to isolate a binding-protein (F29) targeting activated Fyn. Nuclear-magnetic-resonance (NMR) analysis provides the structural basis of F29 specificity for Fyn over homologous SFKs. Using F29, we engineered a sensitive, minimally-perturbing fluorescence-resonance-energy-transfer (FRET) biosensor (FynSensor) that reveals cellular Fyn activity to be spatially localized, pulsatile and sensitive to adhesion/integrin signaling. Strikingly, growth factor stimulation further enhanced Fyn activity in pre-activated intracellular zones. However, inhibition of focal-adhesion-kinase activity not only attenuates Fyn activity, but abolishes growth-factor modulation. FynSensor imaging uncovers spatially-organized, sensitized signaling clusters, direct crosstalk between integrin and growth-factor-signaling, and clarifies how compartmentalized Src-kinase activity may drive cell fate.

scholarly journals FGF signaling dynamics regulates epithelial patterning and morphogenesis

2020 ◽  
Author(s):  
Jakub Sumbal ◽  
Tereza Vranova ◽  
Zuzana Koledova
Keyword(s):  
Growth Factor ◽  
Cell Fate ◽  
Mammary Epithelium ◽  
Time Lapse ◽  
Branching Morphogenesis ◽  
Tissue Level ◽  
Epithelial Tissue ◽  
Growth Factor Signaling ◽  
Fgf Signaling ◽  
Signaling Dynamics

SummarySingle cell assays revealed that growth factor signaling dynamics is actively sensed by a cell and ultimately controls cell fate. However, the effects of growth factor signaling dynamics at the tissue level have been unknown. We used mammary epithelial organoids, time-lapse imaging, fibroblast growth factor 2 (FGF2) variants of different stabilities, mathematical modeling, and perturbation analysis to study the role of FGF2 signaling dynamics in epithelial morphogenesis. We found that fluctuant and sustained FGF signaling dynamics induced distinct morphological and functional states of mammary epithelium through differential employment of intracellular effectors ERK and AKT. ERK activity domains determined epithelial branch size, while AKT activity drove epithelial stratification. Furthermore, FGF signaling dynamics affected epithelial tissue mechanoresponsiveness to extracellular matrix, thereby impinging upon branch elongation. Our study provides new insights into regulation of epithelial patterning and branching morphogenesis by FGF signaling dynamics and into downstream signaling effectors that regulate cellular outcomes.

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