Phosphorylation of adducin-1 by cyclin-dependent kinase 5 is important for epidermal growth factor-induced cell migration

Chia Yi Su, Ruei Liang Yan, Wen Hsin Hsu, Ching Tung Chu, Hsuan Chia Chang, Chien Chen Lai, Hui Ping Hsu, Hong Chen Chen

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

Cyclin-dependent kinase 5 (Cdk5) is predominantly expressed in neuron and plays an important role in neuronal physiology. Increasing evidence also indicates that Cdk5 may contribute to malignant progression of some types of cancers; however, the underlying mechanism remains elusive. In this study, we found that Cdk5 directly phosphorylated the actin-binding protein adducin-1 (ADD1) at T724 in vitro and in intact cells. The capability of the phosphomimetic T724D mutant to bind to actin filaments was lower than that of wild type ADD1 and the T724A mutant. Cdk5 co-localized with ADD1 at the lamellipodia upon epidermal growth factor (EGF) stimulation. The increased lamellipodia formation and cell migration of human breast cancer cells MDA-MB-231 by EGF were accompanied by Cdk5 activation and increased phosphorylation of ADD1 at T724. Depletion of Cdk5 in MDA-MB-231 cells abrogated the effects of EGF on ADD1 T724 phosphorylation, lamellipodia formation, and cell migration. Likewise, depletion of ADD1 suppressed the effects of EGF on lamellipodia formation, cell migration, and invasion, all of which were restored by FLAG-ADD1 WT and the T724D mutant, but not the T724A mutant. Together, our results suggest that phosphorylation of ADD1 at T724 by Cdk5 is important for EGF-induced cell migration and invasion.

Original languageEnglish
Article number13703
JournalScientific reports
Volume9
Issue number1
DOIs
Publication statusPublished - 2019 Dec 1

All Science Journal Classification (ASJC) codes

  • General

Fingerprint Dive into the research topics of 'Phosphorylation of adducin-1 by cyclin-dependent kinase 5 is important for epidermal growth factor-induced cell migration'. Together they form a unique fingerprint.

Cite this