Girdin, a novel actin-binding protein, and its family of proteins possess versatile functions in the Akt and Wnt signaling pathways

Atsushi Enomoto, Jiang Ping, Masahide Takahashi

Research output: Chapter in Book/Report/Conference proceedingConference contribution

73 Citations (Scopus)


Girdin (GIRDers of actIN filament, also reported as APE, GIV, or HkRP1) is a novel protein expressed ubiquitously in mammals and was recently identified as a binding partner of the serine/threonine kinase Akt. We found that Girdin is an actin-binding protein involved in both the remodeling of the actin cytoskeleton and in cell motility. Recent studies have uncovered new and varied functions of Girdin. For example, it prolongs the activation of Akt and regulates DNA replication in response to insulin signaling. Girdin also associates with heterotrimeric G proteins and dynamin (a large GTPase), which are involved in membrane transport. We found that Akt phosphorylates Girdin in response to growth factors such as epidermal growth factor (EGF) in fibroblasts. Furthermore, phosphorylated Girdin accumulates at the leading edge of migrating cells, suggesting its role in Akt-dependent cell migration or tumor invasion. To date, two paralogues of Girdin have been identified in mammals. One of them, Daple (also named HkRP2), is a binding partner and regulator of Dishevelled, an important cytoplasmic component of the Wnt signaling pathway. Another is a protein encoded by FLJ00354 (also named HkRP3), which has not been functionally characterized. These members are assumed to be dimers with large polypeptide chains (220-250 kDa) that associate at their central long coiled-coil domains. The amino acid sequences of the members show about 32-46% overall identity, with the greatest variation toward the carboxyl terminal domains that specify the binding partners. Here we propose roles for this family of proteins in diverse cellular processes.

Original languageEnglish
Title of host publicationIntegrated Molecular Medicine for Neuronal and Neoplastic Disorders
PublisherBlackwell Publishing Inc.
Number of pages16
ISBN (Print)1573316555, 9781573316552
Publication statusPublished - 11-2006
Externally publishedYes

Publication series

NameAnnals of the New York Academy of Sciences
ISSN (Print)0077-8923
ISSN (Electronic)1749-6632

All Science Journal Classification (ASJC) codes

  • General Neuroscience
  • General Biochemistry,Genetics and Molecular Biology
  • History and Philosophy of Science


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