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P21 activated kinase (PAK), PAK interacting exchange factor (PIX), and G protein coupled receptor kinase interactor (GIT) compose a highly conserved signaling module controlling cell migrations, immune system signaling, and the formation of the mammalian nervous system. Traditionally, this signaling module is thought to facilitate the function of RAC and CDC-42 GTPases by allowing for the recruitment of a GTPase effector (PAK), a GTPase activator (PIX), and a scaffolding protein (GIT) as a regulated signaling unit to specific subcellular locations. Instead, we report here that this signaling module functions independently of RAC/CDC-42 GTPases in vivo to control the cell shape and migration of the distal tip cells (DTCs) during morphogenesis of the Caenorhabditis elegans gonad. In addition, this RAC/CDC-42–independent PAK pathway functions in parallel to a classical GTPase/PAK pathway to control the guidance aspect of DTC migration. Among the C. elegans PAKs, only PAK-1 functions in the GIT/PIX/PAK pathway independently of RAC/CDC42 GTPases, while both PAK-1 and MAX-2 are redundantly utilized in the GTPase/PAK pathway. Both RAC/CDC42–dependent and –independent PAK pathways function with the integrin receptors, suggesting that signaling through integrins can control the morphology, movement, and guidance of DTC through discrete pathways. Collectively, our results define a new signaling capacity for the GIT/PIX/PAK module that is likely to be conserved in vertebrates and demonstrate that PAK family members, which are redundantly utilized as GTPase effectors, can act non-redundantly in pathways independent of these GTPases. 相似文献
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Robert R Edwards Ajay D Wasan Clifton O Bingham III Joan Bathon Jennifer A Haythornthwaite Michael T Smith Gayle G Page 《Arthritis research & therapy》2009,11(3):R61-9
Introduction
Maladaptive physiological responses to stress appear to play a role in chronic inflammatory diseases such as rheumatoid arthritis (RA). However, relatively little stress research in RA patients has involved the study of pain, the most commonly reported and most impairing stressor in RA. In the present study, we compared psychophysical and physiological responses to standardized noxious stimulation in 19 RA patients and 21 healthy controls. 相似文献85.
Mehdi Afshari Bavil Zhi Liu Wenzhou Wu Chuanbo Li Buwen Cheng 《Plasmonics (Norwell, Mass.)》2017,12(6):1709-1715
A circular slit-groove surface plasmon polaritons (SPPs) launcher surrounding a photodetector is employed theoretically to enhance the photocurrent of atypical Si-Ge photodetectors. The slit and grooves are designed such that the SPPs are focused at the center of the absorption layer of the photodetector to result in additional electric current. Fabry–Perot resonance condition accurately calculates the period of the groove, slit-groove distance, photodetector radius, and slit-photodetector distance. The manipulation leads to constructive interference between the incident light impinging from the top and the SPPs propagating toward the photodetector. Simulation result shows that photocurrent increases by approximately 13-fold when the SPPs are introduced. 相似文献
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Daw-Yang Hwang Stefan Kohl Xueping Fan Asaf Vivante Stefanie Chan Gabriel C. Dworschak Julian Schulz Albertien M. van Eerde Alina C. Hilger Heon Yung Gee Tracie Pennimpede Bernhard G. Herrmann Glenn van de Hoek Kirsten Y. Renkema Christoph Schell Tobias B. Huber Heiko M. Reutter Neveen A. Soliman Natasa Stajic Radovan Bogdanovic Elijah O. Kehinde Richard P. Lifton Velibor Tasic Weining Lu Friedhelm Hildebrandt 《Human genetics》2015,134(8):905-916
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