TY - JOUR
T1 - Role of the pleckstrin homology domain in intersectin-L Dbl homology domain activation of Cdc42 and signaling
AU - Pruitt, Wendy M.
AU - Karnoub, Antoine E.
AU - Rakauskas, A. Corinne
AU - Guipponi, Michel
AU - Antonarakis, Stylianos E.
AU - Kurakin, Alexei
AU - Kay, Brian K.
AU - Sondek, John
AU - Siderovski, David P.
AU - Der, Channing J.
N1 - Funding Information:
Our research was supported by grants from the National Institutes of Health to C.J.D. (CA63071) and J.S. (GM62299), the Pew Charitable Trusts to J.S., the Swiss Science National Foundation to S.E.A. and from the Leukemia and Lymphoma Society to B.K.K. W.M.P. is supported by a UNCF-Merck Postdoctoral Research Fellowship and D.P.S. is a Year 2000 Neuroscience Scholar of the EJLB Foundation. A.E.K. is a fellow of the Susan G. Komen Breast Cancer Foundation.
PY - 2003/4/7
Y1 - 2003/4/7
N2 - 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.
AB - 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.
KW - Cdc42
KW - Dbl family protein
KW - Dbl homology domain
KW - Phosphatidylinositol 3-kinase
KW - Pleckstrin homology domain
UR - http://www.scopus.com/inward/record.url?scp=0037424854&partnerID=8YFLogxK
U2 - 10.1016/S0167-4889(03)00002-8
DO - 10.1016/S0167-4889(03)00002-8
M3 - Article
C2 - 12676355
AN - SCOPUS:0037424854
SN - 0167-4889
VL - 1640
SP - 61
EP - 68
JO - BBA - Molecular Cell Research
JF - BBA - Molecular Cell Research
IS - 1
ER -