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:2.7.11.27 (
AMPK
)
6,299
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
ACK2
(activated Cdc42-associated tyrosine kinase 2) is a specific downstream effector for Cdc42, a member of the Rho family of small G-proteins.
ACK2
interacts with clathrin, an endocytic vesicle coating protein, and
SH3PX1
, a sorting nexin, and is involved in clathrin-mediated endocytosis. While searching for proteins that interact with
ACK2
, we found that HSP90 (heat-shock protein 90) binds to
ACK2
. Analysis of a series of truncation mutants of
ACK2
has defined the regions within the kinase domain of
ACK2
that are required for binding to HSP90. The binding of HSP90 to
ACK2
is blocked upon treatment with geldanamycin, an HSP90-specific ATPase inhibitor, and is required for the in vivo kinase activity of
ACK2
and its association with Cdc42. Overall, our data suggest a novel mechanism of regulation in which HSP90 serves as a regulatory component in an
ACK2
functional complex and plays a role in sustaining its kinase activity.
...
PMID:Interaction of activated Cdc42-associated tyrosine kinase ACK2 with HSP90. 1514 35
SH3PX1
[SNX9 (
sorting nexin 9
)] is a member of SNX super-family that is recognized by sharing a PX (phox homology) domain. We have previously shown that
SH3PX1
, phosphorylated by
ACK2
(activated Cdc42-associated tyrosine kinase 2), regulates the degradation of EGF (epidermal growth factor) receptor. In mapping the tyrosine phosphorylation region, we found that the C-terminus of
SH3PX1
is required for its tyrosine phosphorylation. Further analysis indicates that this region, known as the coiled-coil domain or the BAR (Bin-amphiphysin-Rvs homology) domain, is the dimerization domain of
SH3PX1
. Truncation of as little as 13 amino acid residues at the very C-terminus in the coiled-coil/BAR domain of
SH3PX1
resulted in no dimerization, no
ACK2
-catalysed and EGF-stimulated tyrosine phosphorylation and no interaction with
ACK2
. The intracellular localization of
SH3PX1
became dysfunctional upon truncation in the BAR domain. Taken together, our results indicate that the dimerization, which is mediated by the BAR domain, is essential for the intracellular function of
SH3PX1
.
...
PMID:Dimerization is required for SH3PX1 tyrosine phosphorylation in response to epidermal growth factor signalling and interaction with ACK2. 1631 19
