Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:3.4.23.5 (
cathepsin D
)
4,130
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
CVAK104
is a novel coated vesicle-associated protein with a serine/threonine kinase homology domain that was recently shown to phosphorylate the beta2-subunit of the adaptor protein (AP) complex AP2 in vitro. Here, we demonstrate that a C-terminal segment of
CVAK104
interacts with the N-terminal domain of clathrin and with the alpha-appendage of AP2.
CVAK104
localizes predominantly to the perinuclear region of HeLa and COS-7 cells, but it is also present on peripheral vesicular structures that are accessible to endocytosed transferrin. The distribution of
CVAK104
overlaps extensively with that of AP1, AP3, the mannose 6-phosphate receptor, and clathrin but not at all with its putative phosphorylation target AP2. RNA interference-mediated clathrin knockdown reduced the membrane association of
CVAK104
. Recruitment of
CVAK104
to perinuclear membranes of permeabilized cells is enhanced by guanosine 5'-O-(3-thio)triphosphate, and brefeldin A redistributes
CVAK104
in cells. Both observations suggest a direct or indirect requirement for GTP-binding proteins in the membrane association of
CVAK104
. Live-cell imaging showed colocalization of green fluorescent protein-
CVAK104
with endocytosed transferrin and with red fluorescent protein-clathrin on rapidly moving endosomes. Like AP1-depleted COS-7 cells,
CVAK104
-depleted cells missort the lysosomal hydrolase
cathepsin D
. Together, our data suggest a function for
CVAK104
in clathrin-dependent pathways between the trans-Golgi network and the endosomal system.
...
PMID:Clathrin-dependent association of CVAK104 with endosomes and the trans-Golgi network. 1691 21
