Role of the pleckstrin homology domain in intersectin-L Dbl homology domain activation of Cdc42 and signaling

Wendy M. Pruitt, Antoine E. Karnoub, A. Corinne Rakauskas, Michel Guipponi, Stylianos E. Antonarakis, Alexei Kurakin, Brian K. Kay, John Sondek, David P. Siderovski, Channing J. Der

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16 Scopus citations

Abstract

Intersectin-long (ITSN-L) contains the invariant Dbl homology (DH) and pleckstrin homology (PH) domain structure characteristic of the majority of Dbl family proteins. This strict domain topography suggests that the PH domain serves an essential, conserved function in the regulation of the intrinsic guanine nucleotide exchange activity of the DH domain. We evaluated the role of the PH domain in regulating the DH domain function of ITSN-L. Surprisingly, we found that the PH domain was dispensable for guanine nucleotide exchange activity on Cdc42 in vitro, yet the PH domain enhanced the ability of the DH domain to activate Cdc42 signaling in vivo. PH domains can interact with phosphoinositide substrates and products of phosphatidylinositol 3-kinase (PI3K). However, PI3K activation did not modulate ITSN-L DH domain function in vivo.

Original languageEnglish
Pages (from-to)61-68
Number of pages8
JournalBiochimica et Biophysica Acta - Molecular Cell Research
Volume1640
Issue number1
DOIs
StatePublished - 7 Apr 2003

Keywords

  • Cdc42
  • Dbl family protein
  • Dbl homology domain
  • Phosphatidylinositol 3-kinase
  • Pleckstrin homology domain

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    Pruitt, W. M., Karnoub, A. E., Rakauskas, A. C., Guipponi, M., Antonarakis, S. E., Kurakin, A., Kay, B. K., Sondek, J., Siderovski, D. P., & Der, C. J. (2003). Role of the pleckstrin homology domain in intersectin-L Dbl homology domain activation of Cdc42 and signaling. Biochimica et Biophysica Acta - Molecular Cell Research, 1640(1), 61-68. https://doi.org/10.1016/S0167-4889(03)00002-8