The homophilic receptor PTPRK selectively dephosphorylates multiple junctional regulators to promote cell-cell adhesion.
Elife
; 82019 03 29.
Article
em En
| MEDLINE
| ID: mdl-30924770
ABSTRACT
Cell-cell communication in multicellular organisms depends on the dynamic and reversible phosphorylation of protein tyrosine residues. The receptor-linked protein tyrosine phosphatases (RPTPs) receive cues from the extracellular environment and are well placed to influence cell signaling. However, the direct events downstream of these receptors have been challenging to resolve. We report here that the homophilic receptor PTPRK is stabilized at cell-cell contacts in epithelial cells. By combining interaction studies, quantitative tyrosine phosphoproteomics, proximity labeling and dephosphorylation assays we identify high confidence PTPRK substrates. PTPRK directly and selectively dephosphorylates at least five substrates, including Afadin, PARD3 and δ-catenin family members, which are all important cell-cell adhesion regulators. In line with this, loss of PTPRK phosphatase activity leads to disrupted cell junctions and increased invasive characteristics. Thus, identifying PTPRK substrates provides insight into its downstream signaling and a potential molecular explanation for its proposed tumor suppressor function.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Adesão Celular
/
Processamento de Proteína Pós-Traducional
/
Proteínas de Ciclo Celular
/
Proteínas Adaptadoras de Transdução de Sinal
/
Células Epiteliais
/
Cateninas
/
Proteínas Tirosina Fosfatases Classe 2 Semelhantes a Receptores
/
Proteínas dos Microfilamentos
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Elife
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Reino Unido