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

Pruitt, W. M.; Karnoub, A. E.; Rakauskas, A. C.; Guipponi, Michel; Antonarakis, Stylianos; Kurakin, Alexei; Kay, B. K.; Sondek, John; Siderovski, D. P.; Der, C. J.

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Title		Role of the pleckstrin homology domain in intersectin-L Dbl homology domain activation of Cdc42 and signaling
Authors		Pruitt, W. M. Karnoub, A. E. Rakauskas, A. C. Guipponi, Michel Antonarakis, Stylianos Kurakin, Alexei Kay, B. K. Sondek, John Siderovski, D. P. Der, C. J. show all authors [1 - 10]
Published in		Biochimica et Biophysica Acta. 2003, vol. 1640, no. 1, p. 61-68
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.
Keywords		Adaptor Proteins, Vesicular Transport — Animals — Blood Proteins/chemistry/genetics/ metabolism — Carrier Proteins/chemistry/genetics/ metabolism — Mice — Phosphoproteins/chemistry/genetics/ metabolism — Protein Isoforms/metabolism — Protein Structure, Tertiary — Signal Transduction — Cdc42 GTP-Binding Protein/ metabolism
Identifiers		DOI: 10.1016/s0167-4889(03)00002-8 PMID: 12676355
Full text		Article - Limited access to UNIGE
Structures		Faculté de médecine / Section de médecine clinique / Département de médecine interne des spécialités
Citation (ISO format)		PRUITT, W. M. et al. Role of the pleckstrin homology domain in intersectin-L Dbl homology domain activation of Cdc42 and signaling. In: Biochimica et Biophysica Acta, 2003, vol. 1640, n° 1, p. 61-68. https://archive-ouverte.unige.ch/unige:8973