DBS is activated by EPHB2/SRC signaling-mediated tyrosine phosphorylation in HEK293 cells.
Mol Cell Biochem
; 459(1-2): 83-93, 2019 Sep.
Article
em En
| MEDLINE
| ID: mdl-31089935
ABSTRACT
It is well known that Rho family small GTPases (Rho GTPase) has a role of molecular switch in intracellular signal transduction. The switch cycle between GTP-bound and GDP-bound state of Rho GTPase regulates various cell responses such as gene transcription, cytoskeletal rearrangements, and vesicular trafficking. Rho GTPase-specific guanine nucleotide exchange factors (RhoGEFs) are regulated by various extracellular stimuli and activates Rho GTPase such as RhoA, Rac1, and Cdc42. The molecular mechanisms that regulate RhoGEFs are poorly understood. Our studies reveal that Dbl's big sister (DBS), a RhoGEF for Cdc42 and RhoA, is phosphorylated at least on tyrosine residues at 479, 660, 727, and 926 upon stimulation by SRC signaling and that the phosphorylation at Tyr-660 is particularly critical for the serum response factor (SRF)-dependent transcriptional activation of DBS by Ephrin type-B receptor 2 (EPHB2)/SRC signaling. In addition, our studies also reveal that the phosphorylation of Tyr-479 and Tyr-660 on DBS leads to the actin cytoskeletal reorganization by EPHB2/SRC signaling. These findings are thought to be useful for understanding pathological conditions related to DBS such as cancer and non-syndromic autism in future.
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Base de dados:
MEDLINE
Assunto principal:
Transdução de Sinais
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Quinases da Família src
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Proteína cdc42 de Ligação ao GTP
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Proteína rhoA de Ligação ao GTP
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Receptor EphB2
Limite:
Humans
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article