Expanding the Disorder-Function Paradigm in the C-Terminal Tails of Erbbs - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Biomolecules Année : 2021

Expanding the Disorder-Function Paradigm in the C-Terminal Tails of Erbbs

Résumé

ErbBs are receptor tyrosine kinases involved not only in development, but also in a wide variety of diseases, particularly cancer. Their extracellular, transmembrane, juxtamembrane, and kinase folded domains were described extensively over the past 20 years, structurally and functionally. However, their whole C-terminal tails (CTs) following the kinase domain were only described at atomic resolution in the last 4 years. They were shown to be intrinsically disordered. The CTs are known to be tyrosine-phosphorylated when the activated homo- or hetero-dimers of ErbBs are formed. Their phosphorylation triggers interaction with phosphotyrosine binding (PTB) or Src Homology 2 (SH2) domains and activates several signaling pathways controling cellular motility, proliferation, adhesion, and apoptosis. Beyond this passive role of phosphorylated domain and site display for partners, recent structural and function studies unveiled active roles in regulation of phosphorylation and interaction: the CT regulates activity of the kinase domain; different phosphorylation states have different compaction levels, potentially modulating the succession of phosphorylation events; and prolines have an important role in structure, dynamics, and possibly regulatory interactions. Here, we review both the canonical role of the disordered CT domains of ErbBs as phosphotyrosine display domains and the recent findings that expand the known range of their regulation functions linked to specific structural and dynamic features.
Fichier principal
Vignette du fichier
Pinet2021_Biomolecules-11-01690-v3.pdf (2.31 Mo) Télécharger le fichier
Origine : Fichiers éditeurs autorisés sur une archive ouverte

Dates et versions

hal-03450673 , version 1 (26-11-2021)

Identifiants

Citer

Louise Pinet, Nadine Assrir, Carine van Heijenoort. Expanding the Disorder-Function Paradigm in the C-Terminal Tails of Erbbs. Biomolecules, 2021, 11, ⟨10.3390/biom11111690⟩. ⟨hal-03450673⟩
9 Consultations
39 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More