Distinct Phosphoinositide Binding Specificity of the GAP1 Family Proteins: Characterization of the Pleckstrin Homology Domains of MRASAL and KIAA0538

2001 ◽  
Vol 288 (1) ◽  
pp. 87-90 ◽  
Author(s):  
Tetsuya Minagawa ◽  
Mitsunori Fukuda ◽  
Katsuhiko Mikoshiba
Keyword(s):  
Binding Specificity ◽  
Pleckstrin Homology ◽  
Homology Domains

scholarly journals A Comparative Analysis of the Phosphoinositide Binding Specificity of Pleckstrin Homology Domains

1997 ◽  
Vol 272 (35) ◽  
pp. 22059-22066 ◽  
Author(s):  
Lucia E. Rameh ◽  
Ann-kristin Arvidsson ◽  
Kermit L. Carraway ◽  
Anthony D. Couvillon ◽  
Gary Rathbun ◽  
...  
Keyword(s):  
Comparative Analysis ◽  
Binding Specificity ◽  
Pleckstrin Homology ◽  
Homology Domains

Structural Characterization of the Interaction between a Pleckstrin Homology Domain and Phosphatidylinositol 4,5-Bisphosphate

Biochemistry ◽  
1995 ◽  
Vol 34 (31) ◽  
pp. 9859-9864 ◽  
Author(s):  
John E. Harlan ◽  
Ho Sup Yoon ◽  
Philip J. Hajduk ◽  
Stephen W. Fesik
Keyword(s):  
Structural Characterization ◽  
Pleckstrin Homology Domain ◽  
Pleckstrin Homology

Pleckstrin homology domains: not just for phosphoinositides

2004 ◽  
Vol 32 (5) ◽  
pp. 707-711 ◽  
Author(s):  
M.A. Lemmon
Keyword(s):  
Subcellular Localization ◽  
Human Genome ◽  
Small Gtpases ◽  
Membrane Targeting ◽  
Ph Domain ◽  
Cellular Membranes ◽  
Pleckstrin Homology ◽  
Ph Domains ◽  
Common Domain ◽  
Homology Domains

PH domains (pleckstrin homology domains) are the 11th most common domain in the human genome and are best known for their ability to target cellular membranes by binding specifically to phosphoinositides. Recent studies in yeast have shown that, in fact, this is a property of only a small fraction of the known PH domains. Most PH domains are not capable of independent membrane targeting, and those capable of doing so (approx. 33%) appear, most often, to require both phosphoinositide and non-phosphoinositide determinants for their subcellular localization. Several recent studies have suggested that small GTPases such as ARF family proteins play a role in defining PH domain localization. Some others have described a signalling role for PH domains in regulating small GTPases, although phosphoinositides may also play a role. These findings herald a change in our perspective of PH domain function, which will be significantly more diverse than previously supposed.

Identification and functional characterization of a novel human protein highly related to the yeast dynamin-like GTPase Vps1p

1998 ◽  
Vol 111 (10) ◽  
pp. 1341-1349 ◽  
Author(s):  
M. Imoto ◽  
I. Tachibana ◽  
R. Urrutia
Keyword(s):  
Endoplasmic Reticulum ◽  
Cho Cells ◽  
Mammalian Cells ◽  
Functional Characterization ◽  
Luciferase Reporter ◽  
Pleckstrin Homology ◽  
Rich Region ◽  
Gtpase Domain ◽  
Proline Rich Region

Dynamin proteins containing a GTPase domain, a pleckstrin homology motif and a proline-rich tail participate in receptor-mediated endocytosis in organisms ranging from insects to vertebrates. In addition, dynamin-related GTPases, such as the yeast Golgi protein Vps1p, which lack both the pleckstrin homology motif and the proline-rich region, participate in vesicular transport within the secretory pathway in lower eukaryotes. However, no data is available on the existence of Vps1p-like proteins in mammalian cells. In this study, we report the identification and characterization of a novel gene encoding a human dynamin-related protein, DRP1, displaying high similarity to the Golgi dynamin-like protein Vps1p from yeast and to a Caenorhabditis elegans protein deposited in the databank. These proteins are highly conserved in their N-terminal tripartite GTPase domain but lack the pleckstrin homology motif and proline-rich region. Northern blot analysis reveals that the DRP1 mRNA is detected at high levels in human muscle, heart, kidney and brain. Immunolocalization studies in Chinese hamster ovary (CHO) cells using an epitope-tagged form of DRP1 and confocal microscopy show that this protein is concentrated in a perinuclear region that labels with the endoplasmic reticulum marker DiOC6(3) and the Golgi marker C5-DMB-Cer. In addition, the localization of DRP1 is highly similar to the localization of the endoplasmic reticulum and cis-Golgi GTPase Rab1A, but not to the staining for the trans-Golgi GTPase Rab6. Furthermore, overexpression of a cDNA encoding a GTP binding site mutant of DRP1 (DRP1(K38E)) in CHO cells decreases the amount of a secreted luciferase reporter protein, whereas the overexpression of wild-type DRP1 increases the secretion of this marker. Together, these results constitute the first structural and functional characterization of a mammalian protein similar to the yeast dynamin-related GTPase Vps1p and indicate that the participation of these proteins in secretion has been conserved throughout evolution.

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