The Cdc42 Target ACK2 Directly Interacts with Clathrin and Influences Clathrin Assembly

Wannian Yang, Charles G. Lo, Thomas Dispenza, Richard A. Cerione

Research output: Contribution to journalArticle

60 Citations (Scopus)

Abstract

The Ras-related GTP-binding protein Cdc42 has been implicated in a diversity of biological functions including the regulation of intracellular trafficking and endocytosis. While screening for Cdc42 targets that influence these activities, we identified the protein-tyrosine kinase ACK2 (for activated Cdc42-associated kinase 2) as a new binding partner for clathrin. ACK2 binds clathrin via a domain that is conserved among a number of other clathrin-binding proteins including the arrestins and AP-2. Overexpression of ACK2 in NIH3T3 cells results in an inhibition of transferrin receptor endocytosis because of a competition between ACK2 and AP-2 for clathrin. Activated Cdc42 weakens the interaction between ACK2 and clathrin and thus reverses the ACK2-mediated inhibition of endocytosis. Overexpression of ACK2 increases the amount of clathrin present in fractions enriched in clathrin-coated vesicles. Taken together, our data suggest that ACK2 may represent a novel clathrin-assembly protein and participate in the regulation of receptor-mediated endocytosis.

Original languageEnglish (US)
Pages (from-to)17468-17473
Number of pages6
JournalJournal of Biological Chemistry
Volume276
Issue number20
DOIs
StatePublished - May 18 2001

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Clathrin
Phosphotransferases
Endocytosis
Vesicular Transport Adaptor Proteins
Arrestins
Clathrin-Coated Vesicles
Transferrin Receptors
Monomeric GTP-Binding Proteins
Biodiversity
Protein-Tyrosine Kinases
Carrier Proteins
Screening

All Science Journal Classification (ASJC) codes

  • Biochemistry

Cite this

Yang, Wannian ; Lo, Charles G. ; Dispenza, Thomas ; Cerione, Richard A. / The Cdc42 Target ACK2 Directly Interacts with Clathrin and Influences Clathrin Assembly. In: Journal of Biological Chemistry. 2001 ; Vol. 276, No. 20. pp. 17468-17473.
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The Cdc42 Target ACK2 Directly Interacts with Clathrin and Influences Clathrin Assembly. / Yang, Wannian; Lo, Charles G.; Dispenza, Thomas; Cerione, Richard A.

In: Journal of Biological Chemistry, Vol. 276, No. 20, 18.05.2001, p. 17468-17473.

Research output: Contribution to journalArticle

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