scholarly journals Antagonists of phosphatidylinositol 3-kinase block activation of several novel protein kinases in neutrophils

1995 ◽  
Vol 270 (19) ◽  
pp. 11684-11691 ◽  
Author(s):  
J Ding ◽  
CJ Vlahos ◽  
R Liu ◽  
RF Brown ◽  
JA Badwey
Keyword(s):  
Protein Kinases ◽  
Phosphatidylinositol 3 Kinase ◽  
Novel Protein ◽  
Phosphatidylinositol 3

scholarly journals Rabenosyn-5, a Novel Rab5 Effector, Is Complexed with Hvps45 and Recruited to Endosomes through a Fyve Finger Domain

2000 ◽  
Vol 151 (3) ◽  
pp. 601-612 ◽  
Author(s):  
Erik Nielsen ◽  
Savvas Christoforidis ◽  
Sandrine Uttenweiler-Joseph ◽  
Marta Miaczynska ◽  
Frederique Dewitte ◽  
...  
Keyword(s):  
Early Endosome ◽  
Effector Proteins ◽  
Endosomal Trafficking ◽  
Membrane Domains ◽  
Phosphatidylinositol 3 Kinase ◽  
Early Endosomes ◽  
Site Of Action ◽  
Endosomal Membranes ◽  
Novel Protein ◽  
Phosphatidylinositol 3

Rab5 regulates endocytic membrane traffic by specifically recruiting cytosolic effector proteins to their site of action on early endosomal membranes. We have characterized a new Rab5 effector complex involved in endosomal fusion events. This complex includes a novel protein, Rabenosyn-5, which, like the previously characterized Rab5 effector early endosome antigen 1 (EEA1), contains an FYVE finger domain and is recruited in a phosphatidylinositol-3-kinase–dependent fashion to early endosomes. Rabenosyn-5 is complexed to the Sec1-like protein hVPS45. hVPS45 does not interact directly with Rab5, therefore Rabenosyn-5 serves as a molecular link between hVPS45 and the Rab5 GTPase. This property suggests that Rabenosyn-5 is a closer mammalian functional homologue of yeast Vac1p than EEA1. Furthermore, although both EEA1 and Rabenosyn-5 are required for early endosomal fusion, only overexpression of Rabenosyn-5 inhibits cathepsin D processing, suggesting that the two proteins play distinct roles in endosomal trafficking. We propose that Rab5-dependent formation of membrane domains enriched in phosphatidylinositol-3-phosphate has evolved as a mechanism for the recruitment of multiple effector proteins to mammalian early endosomes, and that these domains are multifunctional, depending on the differing activities of the effector proteins recruited.

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