The Rho family GEF FARP2 is activated by aPKCι to control tight junction formation and polarity.
J Cell Sci
; 132(8)2019 04 25.
Article
en En
| MEDLINE
| ID: mdl-30872454
ABSTRACT
The elaboration of polarity is central to organismal development and to the maintenance of functional epithelia. Among the controls determining polarity are the PAR proteins, PAR6, aPKCι and PAR3, regulating both known and unknown effectors. Here, we identify FARP2 as a 'RIPR' motif-dependent partner and substrate of aPKCι that is required for efficient polarisation and junction formation. Binding is conferred by a FERM/FA domain-kinase domain interaction and detachment promoted by aPKCι-dependent phosphorylation. FARP2 is shown to promote GTP loading of Cdc42, which is consistent with it being involved in upstream regulation of the polarising PAR6-aPKCι complex. However, we show that aPKCι acts to promote the localised activity of FARP2 through phosphorylation. We conclude that this aPKCι-FARP2 complex formation acts as a positive feedback control to drive polarisation through aPKCι and other Cdc42 effectors.This article has an associated First Person interview with the first author of the paper.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Proteína Quinasa C
/
Uniones Estrechas
/
Proteína de Unión al GTP cdc42
/
Factores de Intercambio de Guanina Nucleótido
/
Células Epiteliales
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
J Cell Sci
Año:
2019
Tipo del documento:
Article
País de afiliación:
Reino Unido