Advances in Understanding TKS4 and TKS5: Molecular Scaffolds Regulating Cellular Processes from Podosome and Invadopodium Formation to Differentiation and Tissue Homeostasis

Gyöngyi Kudlik, Tamás Takács, László Radnai, Anita Kurilla, Bálint Szeder, Kitti Koprivanacz, Balázs L. Merő, László Buday, Virag Vas (Lead / Corresponding author)

Research output: Contribution to journalArticlepeer-review

8 Downloads (Pure)

Abstract

Scaffold proteins are typically thought of as multi-domain “bridging molecules.” They serve as crucial regulators of key signaling events by simultaneously binding multiple participants involved in specific signaling pathways. In the case of epidermal growth factor (EGF)-epidermal growth factor receptor (EGFR) binding, the activated EGFR contacts cytosolic SRC tyrosine-kinase, which then becomes activated. This process leads to the phosphorylation of SRC-substrates, including the tyrosine kinase substrates (TKS) scaffold proteins. The TKS proteins serve as a platform for the recruitment of key players in EGFR signal transduction, promoting cell spreading and migration. The TKS4 and the TKS5 scaffold proteins are tyrosine kinase substrates with four or five SH3 domains, respectively. Their structural features allow them to recruit and bind a variety of signaling proteins and to anchor them to the cytoplasmic surface of the cell membrane. Until recently, TKS4 and TKS5 had been recognized for their involvement in cellular motility, reactive oxygen species-dependent processes, and embryonic development, among others. However, a number of novel functions have been discovered for these molecules in recent years. In this review, we attempt to cover the diverse nature of the TKS molecules by discussing their structure, regulation by SRC kinase, relevant signaling pathways, and interaction partners, as well as their involvement in cellular processes, including migration, invasion, differentiation, and adipose tissue and bone homeostasis. We also describe related pathologies and the established mouse models.

Original languageEnglish
Article number8117
Number of pages28
JournalInternational Journal of Molecular Sciences
Volume21
Issue number21
DOIs
Publication statusPublished - 30 Oct 2020

Keywords

  • Adipose tissue
  • Bone homeostasis
  • Epithelial–mesenchymal transition
  • Invasion
  • Mesenchymal stem cells
  • Scaffold protein
  • TKS4
  • TKS5
  • Tyrosine kinase substrates

Fingerprint Dive into the research topics of 'Advances in Understanding TKS4 and TKS5: Molecular Scaffolds Regulating Cellular Processes from Podosome and Invadopodium Formation to Differentiation and Tissue Homeostasis'. Together they form a unique fingerprint.

Cite this