Parsons, M. et al. (2005) Spatially distinct binding of Cdc42 to PAK1 and N-WASP in breast carcinoma cells. Molecular and Cellular Biology, 25(5), pp. 1680-1695. (doi: 10.1128/MCB.25.5.1680-1695.2005) (PMID:15713627) (PMCID:PMC549353)
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Abstract
While a significant amount is known about the biochemical signaling pathways of the Rho family GTPase Cdc42, a better understanding of how these signaling networks are coordinated in cells is required. In particular, the predominant subcellular sites where GTP-bound Cdc42 binds to its effectors, such as p21-activated kinase 1 (PAK1) and N-WASP, a homolog of the Wiskott-Aldritch syndrome protein, are still undetermined. Recent fluorescence resonance energy transfer (FRET) imaging experiments using activity biosensors show inconsistencies between the site of local activity of PAK1 or N-WASP and the formation of specific membrane protrusion structures in the cell periphery. The data presented here demonstrate the localization of interactions by using multiphoton time-domain fluorescence lifetime imaging microscopy (FLIM). Our data here establish that activated Cdc42 interacts with PAK1 in a nucleotide-dependent manner in the cell periphery, leading to Thr-423 phosphorylation of PAK1, particularly along the lengths of cell protrusion structures. In contrast, the majority of GFP-N-WASP undergoing FRET with Cy3-Cdc42 is localized within a transferrin receptor- and Rab11-positive endosomal compartment in breast carcinoma cells. These data reveal for the first time distinct spatial association patterns between Cdc42 and its key effector proteins controlling cytoskeletal remodeling.
Item Type: | Articles |
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Status: | Published |
Refereed: | Yes |
Glasgow Author(s) Enlighten ID: | Machesky, Professor Laura |
Authors: | Parsons, M., Monypenny, J., Ameer-Beg, S. M., Millard, T. H., Machesky, L. M., Peter, M., Keppler, M. D., Schiavo, G., Watson, R., Chernoff, J., Zicha, D., Vojnovic, B., and Ng, T. |
College/School: | College of Medical Veterinary and Life Sciences > School of Cancer Sciences |
Journal Name: | Molecular and Cellular Biology |
Publisher: | American Society for Microbiology |
ISSN: | 0270-7306 |
ISSN (Online): | 1098-5549 |
Published Online: | 25 December 2020 |
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