scholarly journals The role of ciliary trafficking in Hedgehog receptor signaling

2015 ◽  
Vol 8 (379) ◽  
pp. ra55-ra55 ◽  
Author(s):  
Jynho Kim ◽  
Elaine Y. C. Hsia ◽  
Amira Brigui ◽  
Anne Plessis ◽  
Philip A. Beachy ◽  
...  
Keyword(s):  
Receptor Signaling

scholarly journals SAT-604 The Role of the Focal Adhesion Kinase Family in Leptin Receptor Signaling

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Colleen Hadley ◽  
Isin Cakir ◽  
Roger D Cone
Keyword(s):  
Food Intake ◽  
Focal Adhesion Kinase ◽  
Focal Adhesion ◽  
Leptin Receptor ◽  
Kinase Activity ◽  
Cytokine Receptor ◽  
Receptor Signaling ◽  
Kinase Family ◽  
Stat3 Phosphorylation

Abstract Overweight and obesity are global concerns affecting nearly one third of the world population. These conditions are characterized by increased adiposity and are accompanied by a proportional increase in circulating leptin, an anorexigenic adipokine. Leptin is responsible for signaling peripheral energy status to the central nervous system to modulate food intake and energy expenditure. As such, neurons within the hypothalamus expressing the long isoform of leptin receptor (LepRb), a type I cytokine receptor, are primarily responsible for mediating the effects of leptin, which signal predominantly through the JAK2-STAT3 transduction mechanism. STAT3 is a latent transcription factor activated upon phosphorylation, which triggers its homodimerization and nuclear translocation. Evidence, however, for JAK2-independent, STAT3-dependent leptin receptor signaling mechanisms exist. FAK (focal adhesion kinase, Ptk2) and Pyk2 (protein tyrosine kinase 2b, Ptk2b) are a subset of nonreceptor protein tyrosine kinases and comprise the focal adhesion kinase family. FAK and Pyk2 are implicated in the regulation of cytokine receptor signaling. Furthermore, Pyk2 knockout mice have an obesity prone phenotype. Here, we studied the role of the focal adhesion kinases in leptin receptor signaling using genetic and pharmacological approaches. We found that overexpression of Pyk2 or FAK increased STAT3 phosphorylation (activation). Overexpression of a FAK or Pyk2 construct with impaired kinase activity, however, attenuated STAT3 phosphorylation, suggesting the increase in STAT3 phosphorylation is largely dependent upon kinase activity of FAK/Pyk2. Treatment of cells with a small molecule dual inhibitor of FAK and Pyk2 (PF431396) attenuated leptin-induced STAT3 phosphorylation in a mouse hypothalamic cell line. Importantly, this effect is independent of JAK2, as PF treatment of two independent JAK2-deficient cell lines exhibited similar attenuation of leptin-induced STAT3 phosphorylation. To assess the physiological relevance of FAK/Pyk2 in leptin receptor signaling in vivo, we administered PF compound to the lateral ventricle of 24-hour fasted lean wild-type mice followed by peripheral leptin administration. Intracerebroventricular (ICV) administration of PF suppressed the anorectic effect of leptin as evidenced by impaired inhibition of food intake upon refeeding. Accordingly, analysis of total hypothalamic lysates from these mice showed ICV PF impaired leptin-induced STAT3 phosphorylation. Taken together, these data suggest that Pyk2 and/or FAK play a role in leptin signal transduction.

scholarly journals Dual Role of the Tyrosine Kinase Syk in Regulation of Toll-Like Receptor Signaling in Plasmacytoid Dendritic Cells

PLoS ONE ◽  
2016 ◽  
Vol 11 (6) ◽  
pp. e0156063 ◽  
Author(s):  
Besma Aouar ◽  
Denisa Kovarova ◽  
Sebastien Letard ◽  
Albert Font-Haro ◽  
Jonathan Florentin ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Tyrosine Kinase ◽  
Plasmacytoid Dendritic Cells ◽  
Dual Role ◽  
Receptor Signaling ◽  
Toll Like Receptor

scholarly journals Deciphering the Novel Role of Gαz in Mu Opioid Receptor Signaling

2021 ◽  
Vol 35 (S1) ◽  
Author(s):  
Miriam Barnett ◽  
Brian Knapp ◽  
Jean Bidlack
Keyword(s):  
Opioid Receptor ◽  
Mu Opioid Receptor ◽  
The Novel ◽  
Receptor Signaling ◽  
Mu Opioid

scholarly journals Diminished Role of Dopamine D1-Receptor Signaling with the Development of an Addicted Phenotype in Rats

2014 ◽  
Vol 76 (1) ◽  
pp. 8-14 ◽  
Author(s):  
Carolina P. Ramôa ◽  
Susan E. Doyle ◽  
Matthew D. Lycas ◽  
Andrea K. Chernau ◽  
Wendy J. Lynch
Keyword(s):  
Dopamine D1 Receptor ◽  
D1 Receptor ◽  
Receptor Signaling
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