Tks5 SH3 domains exhibit differential effects on invadopodia development
| Autor: | Kelley Whitaker, Maryam Ahmed, Joseph Breeyear, Brewer Logan, Darren F. Seals, Christina Daly |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Male
Biochemistry SH3 domain 0302 clinical medicine Cell Movement Animal Products Phosphorylation Post-Translational Modification Staining 0303 health sciences Multidisciplinary biology Chemistry Cell Staining Agriculture Cell biology Gene Expression Regulation Neoplastic Laboratory Equipment src-Family Kinases 030220 oncology & carcinogenesis Invadopodia Podosomes Engineering and Technology Medicine Biological Cultures Cellular Structures and Organelles Cortactin Proto-oncogene tyrosine-protein kinase Src Research Article Endosome Imaging Techniques Science Protein domain Equipment Endosomes Research and Analysis Methods Gelatin Media src Homology Domains 03 medical and health sciences Protein Domains Cell Line Tumor LNCaP Fluorescence Imaging Genetics Humans Point Mutation Protein Interaction Domains and Motifs Vesicles 030304 developmental biology Carcinoma Prostatic Neoplasms Biology and Life Sciences Proteins Cell Biology Fibroblasts Culture Media Adaptor Proteins Vesicular Transport Specimen Preparation and Treatment Mutation biology.protein Gelatin |
| Zdroj: | PLoS ONE, Vol 15, Iss 1, p e0227855 (2020) PLoS ONE |
| ISSN: | 1932-6203 |
| Popis: | The Src substrate Tks5 helps scaffold matrix-remodeling invadopodia in invasive cancer cells. Focus was directed here on how the five SH3 domains of Tks5 impact that activity. Mutations designed to inhibit protein-protein interactions were created in the individual SH3 domains of Tks5, and the constructs were introduced into the LNCaP prostate carcinoma cell line, a model system with intrinsically low Tks5 expression and which our lab had previously showed the dependence of Src-dependent Tks5 phosphorylation on invadopodia development. In LNCaP cells, acute increases in wild-type Tks5 led to increased gelatin matrix degradation. A similar result was observed when Tks5 was mutated in its 4th or 5th SH3 domains. This was in contrast to the 1st, 2nd, and 3rd SH3 domain mutations of Tks5 where each had a remarkable accentuating effect on gelatin degradation. Conversely, in the invadopodia-competent Src-3T3 model system, mutations in any one of the first three SH3 domains had a dominant negative effect that largely eliminated the presence of invadopodia, inhibited gelatin degradation activity, and redistributed both Src, cortactin, and Tks5 to what are likely endosomal compartments. A hypothesis involving Tks5 conformational states and the regulation of endosomal trafficking is presented as an explanation for these seemingly disparate results. |
| Databáze: | OpenAIRE |
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