scholarly journals Unconventional Estrogen Signaling in Health and Disease

Endocrinology ◽  
2020 ◽  
Vol 161 (4) ◽  
Author(s):  
Christina L Faltas ◽  
Kira A LeBron ◽  
Marina K Holz
Keyword(s):  
Gene Expression ◽  
Cell Growth ◽  
Estrogen Receptors ◽  
Signaling Pathways ◽  
Estrogen Signaling ◽  
Estrogen Activity ◽  
Health And Disease ◽  
Males And Females ◽  
Cell Growth And Proliferation ◽  
Cytoplasmic Signaling

Abstract Estrogen is a key hormone involved in the development and homeostasis of several tissue types in both males and females. By binding estrogen receptors, estrogen regulates essential functions of gene expression, metabolism, cell growth, and proliferation by acting through cytoplasmic signaling pathways or activating transcription in the nucleus. However, disruption or dysregulation of estrogen activity has been shown to play a key role in the pathogenesis and progression of many diseases. This review will expatiate on some of the unconventional roles of estrogen in homeostasis and disease.

scholarly journals Activation of the essential kinase PDK1 by phosphoinositide-driven autophosphorylation

2021 ◽  
Author(s):  
Aleksandra Levina ◽  
Kaelin D Fleming ◽  
John E Burke ◽  
Thomas A Leonard
Keyword(s):  
Protein Kinase ◽  
Cell Growth ◽  
Signaling Pathways ◽  
Protein Kinases ◽  
Crucial Role ◽  
Ph Domain ◽  
Face To Face ◽  
Regulatory Motifs ◽  
Positive Cooperativity ◽  
Cell Growth And Proliferation

3-phosphoinositide-dependent kinase 1 (PDK1) is an essential serine/threonine protein kinase, which plays a crucial role in cell growth and proliferation. It is often referred to as a master kinase due to its ability to activate at least 23 downstream protein kinases implicated in various signaling pathways. In this study, we have elucidated the mechanism of phosphoinositide-driven PDK1 auto-activation. We show that PDK1 trans-autophosphorylation is mediated by a PIP3-mediated face-to-face dimer. We report regulatory motifs in the kinase-PH interdomain linker that allosterically activate PDK1 autophosphorylation via a linker-swapped dimer mechanism. Finally, we show that PDK1 is autoinhibited by its PH domain and that positive cooperativity of PIP3 binding drives switch-like activation of PDK1. Our work implies that the PDK1-mediated activation of effector kinases, including Akt, PKC, Sgk, S6K and RSK, many of whom are not directly regulated by phosphoinositides, is also likely to be dependent on PIP3 or PI(3,4)P2.

MAP KINASE SIGNALING PATHWAYS DIFFERENTIALLY AFFECT CELL GROWTH AND PROLIFERATION OF INVASIVE BLADDER CANCER CELLS

2009 ◽  
Vol 181 (4S) ◽  
pp. 344-344
Author(s):  
Jane Peterson ◽  
Binod Kumar ◽  
Sweaty Koul ◽  
Lakshmipathi Khandrika ◽  
Shandra Wilson ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cell Growth ◽  
Map Kinase ◽  
Cancer Cells ◽  
Signaling Pathways ◽  
Invasive Bladder Cancer ◽  
Kinase Signaling ◽  
Bladder Cancer Cells ◽  
Cell Growth And Proliferation ◽  
Affect Cell Growth

Retinal gene expression shows compartment specific differences in health and disease

2014 ◽  
Vol 9 (S 01) ◽  
Author(s):  
C Weinold ◽  
M Kolibabka ◽  
G Molema ◽  
D Margerie ◽  
HP Hammes
Keyword(s):  
Gene Expression ◽  
Health And Disease
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