scholarly journals Critical Role of the Pleckstrin Homology Domain in Dbs Signaling and Growth Regulation

2003 ◽  
Vol 278 (23) ◽  
pp. 21188-21196 ◽  
Author(s):  
Ernesto J. Fuentes ◽  
Antoine E. Karnoub ◽  
Michelle A. Booden ◽  
Channing J. Der ◽  
Sharon L. Campbell
Keyword(s):  
Growth Regulation ◽  
Critical Role ◽  
Pleckstrin Homology Domain ◽  
Pleckstrin Homology

scholarly journals Inhibition of Ca2+ signalling by p130, a phospholipase-C-related catalytically inactive protein: critical role of the p130 pleckstrin homology domain

2000 ◽  
Vol 349 (1) ◽  
pp. 357 ◽  
Author(s):  
Hiroshi TAKEUCHI ◽  
Masahiro OIKE ◽  
Hugh F. PATERSON ◽  
Victoria ALLEN ◽  
Takashi KANEMATSU ◽  
...  
Keyword(s):  
Phospholipase C ◽  
Critical Role ◽  
Pleckstrin Homology Domain ◽  
Pleckstrin Homology ◽  
Inactive Protein

scholarly journals Critical Role for Kalirin in Nerve Growth Factor Signaling through TrkA

2005 ◽  
Vol 25 (12) ◽  
pp. 5106-5118 ◽  
Author(s):  
Kausik Chakrabarti ◽  
Rong Lin ◽  
Noraisha I. Schiller ◽  
Yanping Wang ◽  
David Koubi ◽  
...  
Keyword(s):  
Nerve Growth Factor ◽  
Growth Factor ◽  
Pc12 Cells ◽  
Critical Role ◽  
Neuronal Morphology ◽  
Neurotrophin Receptor ◽  
General Mechanism ◽  
Pleckstrin Homology Domain ◽  
Pleckstrin Homology ◽  
Nerve Growth

ABSTRACT Kalirin is a multidomain guanine nucleotide exchange factor (GEF) that activates Rho proteins, inducing cytoskeletal rearrangement in neurons. Although much is known about the effects of Kalirin on Rho GTPases and neuronal morphology, little is known about the association of Kalirin with the receptor/signaling systems that affect neuronal morphology. Our experiments demonstrate that Kalirin binds to and colocalizes with the TrkA neurotrophin receptor in neurons. In PC12 cells, inhibition of Kalirin expression using antisense RNA decreased nerve growth factor (NGF)-induced TrkA autophosphorylation and process extension. Kalirin overexpression potentiated neurotrophin-stimulated TrkA autophosphorylation and neurite outgrowth in PC12 cells at a low concentration of NGF. Furthermore, elevated Kalirin expression resulted in catalytic activation of TrkA, as demonstrated by in vitro kinase assays and increased NGF-stimulated cellular activation of Rac, Mek, and CREB. Domain mapping demonstrated that the N-terminal Kalirin pleckstrin homology domain mediates the interaction with TrkA. The effects of Kalirin on TrkA provide a molecular basis for the requirement of Kalirin in process extension from PC12 cells and for previously observed effects on axonal extension and dendritic maintenance. The interaction of TrkA with the pleckstrin homology domain of Kalirin may be one example of a general mechanism whereby receptor/Rho GEF pairings play an important role in receptor tyrosine kinase activation and signal transduction.

Novel role of pleckstrin homology domain of the Bcr-Abl protein: Analysis of protein–protein and protein–lipid interactions

2010 ◽  
Vol 316 (4) ◽  
pp. 530-542 ◽  
Author(s):  
Daria Miroshnychenko ◽  
Anna Dubrovska ◽  
Stanislav Maliuta ◽  
Gennady Telegeev ◽  
Pontus Aspenström
Keyword(s):  
Protein Analysis ◽  
Pleckstrin Homology Domain ◽  
Pleckstrin Homology ◽  
Lipid Interactions

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

2003 ◽  
Vol 1640 (1) ◽  
pp. 61-68 ◽  
Author(s):  
Wendy M. Pruitt ◽  
Antoine E. Karnoub ◽  
A.Corinne Rakauskas ◽  
Michel Guipponi ◽  
Stylianos E. Antonarakis ◽  
...  
Keyword(s):  
Pleckstrin Homology Domain ◽  
Pleckstrin Homology ◽  
Dbl Homology Domain

scholarly journals Role of Pleckstrin Homology Domain in Regulating Membrane Targeting and Metabolic Function of Insulin Receptor Substrate 3

2003 ◽  
Vol 17 (8) ◽  
pp. 1568-1579 ◽  
Author(s):  
Tania Maffucci ◽  
Giorgia Razzini ◽  
Alessandra Ingrosso ◽  
Hui Chen ◽  
Stefano Iacobelli ◽  
...  
Keyword(s):  
Insulin Receptor ◽  
Pleckstrin Homology Domain ◽  
Membrane Targeting ◽  
Insulin Receptor Substrate ◽  
Metabolic Function ◽  
Pleckstrin Homology

scholarly journals Structural and Functional Determinants of Conserved Lipid Interaction Domains of Inward Rectifying Kir6.2 Channels

2002 ◽  
Vol 119 (6) ◽  
pp. 581-591 ◽  
Author(s):  
Catherine A. Cukras ◽  
Iana Jeliazkova ◽  
Colin G. Nichols
Keyword(s):  
Critical Role ◽  
Katp Channels ◽  
Pleckstrin Homology Domain ◽  
Membrane Association ◽  
Kir Channel ◽  
M1 Receptor ◽  
Interaction Domains ◽  
Mechanistic Basis ◽  
Α Helix

All members of the inward rectifiier K+ (Kir) channel family are activated by phosphoinositides and other amphiphilic lipids. To further elucidate the mechanistic basis, we examined the membrane association of Kir6.2 fragments of KATP channels, and the effects of site-directed mutations of these fragments and full-length Kir6.2 on membrane association and KATP channel activity, respectively. GFP-tagged Kir6.2 COOH terminus and GFP-tagged pleckstrin homology domain from phospholipase C δ1 both associate with isolated membranes, and association of each is specifically reduced by muscarinic m1 receptor–mediated phospholipid depletion. Kir COOH termini are predicted to contain multiple β-strands and a conserved α-helix (residues ∼306–311 in Kir6.2). Systematic mutagenesis of D307-F315 reveals a critical role of E308, I309, W311 and F315, consistent with residues lying on one side of a α-helix. Together with systematic mutation of conserved charges, the results define critical determinants of a conserved domain that underlies phospholipid interaction in Kir channels.

Inhibition of Ca2+ signalling by p130, a phospholipase-C-related catalytically inactive protein: critical role of the p130 pleckstrin homology domain

2000 ◽  
Vol 349 (1) ◽  
pp. 357-368 ◽  
Author(s):  
Hiroshi TAKEUCHI ◽  
Masahiro OIKE ◽  
Hugh F. PATERSON ◽  
Victoria ALLEN ◽  
Takashi KANEMATSU ◽  
...  
Keyword(s):  
Phospholipase C ◽  
Cellular Localization ◽  
Critical Role ◽  
Inhibitory Effect ◽  
Pleckstrin Homology Domain ◽  
Pleckstrin Homology ◽  
Ligand Complex ◽  
Epidermal Growth ◽  
In Cells

p130 was originally identified as an Ins(1,4,5)P3-binding protein similar to phospholipase C-∆ but lacking any phospholipase activity. In the present study we have further analysed the interactions of p130 with inositol compounds in vitro. To determine which of the potential ligands interacts with p130 in cells, we performed an analysis of the cellular localization of this protein, the isolation of a protein-ligand complex from cell lysates and studied the effects of p130 on Ins(1,4,5)P3-mediated Ca2+ signalling by using permeabilized and transiently or stably transfected COS-1 cells (COS-1p130). In vitro, p130 bound Ins(1,4,5)P3 with a higher affinity than that for phosphoinositides. When the protein was isolated from COS-1p130 cells by immunoprecipitation, it was found to be associated with Ins(1,4,5)P3. Localization studies demonstrated the presence of the full-length p130 in the cytoplasm of living cells, not at the plasma membrane. In cell-based assays, p130 had an inhibitory effect on Ca2+ signalling. When fura-2-loaded COS-1p130 cells were stimulated with bradykinin, epidermal growth factor or ATP, it was found that the agonist-induced increase in free Ca2+ concentration, observed in control cells, was inhibited in COS-1p130. This inhibition was not accompanied by the decreased production of Ins(1,4,5)P3; the intact p130 pleckstrin homology domain, known to be the ligand-binding site in vitro, was required for this effect in cells. These results suggest that Ins(1,4,5)P3 could be the main p130 ligand in cells and that this binding has the potential to inhibit Ins(1,4,5)P3-mediated Ca2+ signalling.

scholarly journals Regulation of Insulin Receptor Substrate 1 Pleckstrin Homology Domain by Protein Kinase C: Role of Serine 24 Phosphorylation

2006 ◽  
Vol 20 (8) ◽  
pp. 1838-1852 ◽  
Author(s):  
Ranmali Nawaratne ◽  
Alexander Gray ◽  
Christina H. Jørgensen ◽  
C. Peter Downes ◽  
Kenneth Siddle ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Insulin Receptor ◽  
Pleckstrin Homology Domain ◽  
Insulin Receptor Substrate ◽  
Pleckstrin Homology ◽  
Insulin Receptor Substrate 1 ◽  
Kinase C

scholarly journals Essential Role of the Dynamin Pleckstrin Homology Domain in Receptor-Mediated Endocytosis

1999 ◽  
Vol 19 (2) ◽  
pp. 1410-1415 ◽  
Author(s):  
Mircea Achiriloaie ◽  
Barbara Barylko ◽  
Joseph P. Albanesi
Keyword(s):  
Cultured Cells ◽  
Pleckstrin Homology Domain ◽  
Heterotrimeric G Proteins ◽  
Ph Domain ◽  
Pleckstrin Homology ◽  
Point Mutant ◽  
Associated Proteins ◽  
Transferrin Uptake

ABSTRACT Pleckstrin homology (PH) domains are found in numerous membrane-associated proteins and have been implicated in the mediation of protein-protein and protein-phospholipid interactions. Dynamin, a GTPase required for clathrin-dependent endocytosis, contains a PH domain which binds to phosphoinositides and participates in the interaction between dynamin and the βγ subunits of heterotrimeric G proteins. The PH domain is essential for expression of phosphoinositide-stimulated GTPase activity of dynamin in vitro, but its involvement in the endocytic process is unknown. We expressed a series of dynamin PH domain mutants in cultured cells and determined their effect on transferrin uptake by those cells. Endocytosis is blocked in cells expressing a PH domain deletion mutant and a point mutant that fails to interact with phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2]. In contrast, expression of a point mutant with unimpaired PI(4,5)P2 interaction has no effect on transferrin uptake. These results demonstrate the significance of the PH domain for dynamin function and suggest that its role may be to mediate interactions between dynamin and phosphoinositides.

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