Role of the pleckstrin homology domain in intersectin-L Dbl homology domain activation of Cdc42 and signaling.
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.
Pruitt
Wendy M
WM
Department of Pharmacology and Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7295, USA.
Karnoub
Antoine E
AE
Rakauskas
A Corinne
AC
Guipponi
Michel
M
Antonarakis
Stylianos E
SE
Kurakin
Alexei
A
Kay
Brian K
BK
Sondek
John
J
Siderovski
David P
DP
Der
Channing J
CJ
D016475:3T3 Cells; D033942:Adaptor Proteins, Vesicular Transport; D000818:Animals; D001798:Blood Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010750:Phosphoproteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D020033:Protein Isoforms / Q000378:metabolism; D017434:Protein Structure, Tertiary; D015398:Signal Transduction; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism*
D033942:Adaptor Proteins, Vesicular Transport; D001798:Blood Proteins; D002352:Carrier Proteins; D010750:Phosphoproteins; D020033:Protein Isoforms; C115919:intersectin 1; C039077:platelet protein P47; D019869:Phosphatidylinositol 3-Kinases; D020764:cdc42 GTP-Binding Protein