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:2.7.11.1 (
protein kinase
)
81,284
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Barrier function and transepithelial transport are intimately linked and are sometimes disturbed in parallel. DRA (downregulated in adenoma) is an intestinal chloride/bicarbonate exchanger that is functionally coupled to CFTR (cystic fibrosis transmembrane regulator) in the upper gastrointestinal tract to mediate chloride and bicarbonate secretion and to NHE3 (Na/H exchanger- isoform 3) in the lower gastrointestinal tract to mediate electroneutral NaCl absorption. All three transport proteins possess PDZ domain binding motifs that facilitate binding to members of the NHERF (Na/H exchanger regulatory factor) family of adapter proteins [NHERF, E3KARP (NHE3 kinase A regulatory protein), PDZK1 (PDZ protein kidney 1) and IKEPP (
intestinal and kidney enriched PDZ protein
)]. Regulation of DRA appears to depend on the presence of a partner transport protein, and this may involve the assembly of different complexes of transporters, adapter proteins, and signaling molecules. We have established stable expression of DRA in HEK cells. In these cells, that do not express significant amounts of CFTR or NHE3, DRA is inhibited by intracellular calcium but not by protein kinase C or
protein kinase A
. At high calcium concentrations induced by 4Br-A23187 this inhibition is independent of the PDZ interaction of DRA. These data show that DRA can be individually regulated and may be confirmed in a more physiologically relevant expression system (i.e., Caco-2/BBE cells) using natural agonists of the intracellular calcium signal.
...
PMID:Regulation of the intestinal anion exchanger DRA (downregulated in adenoma). 1953 14
Prostacyclin and its I prostanoid receptor, the IP, play central roles in hemostasis and in re-endothelialization in response to vascular injury. Herein,
intestinal and kidney enriched PDZ protein
(
IKEPP
) was identified as an interactant of the human (h) IP mediated through binding of PDZ domain 1 (PDZ(D1)) and, to a lesser extent, PDZ(D2) of
IKEPP
to a carboxyl-terminal Class I 'PDZ ligand' within the hIP. While the interaction is constitutive, agonist-activation of the hIP leads to
cAMP-dependent protein kinase
(PK) A and PKC-phosphorylation of
IKEPP
, coinciding with its increased interaction with the hIP. Ectopic expression of
IKEPP
increases functional expression of the hIP, enhancing its ligand binding and agonist-induced cAMP generation. Originally thought to be restricted to renal and gastrointestinal tissues, herein,
IKEPP
was also found to be expressed in vascular endothelial cells where it co-localizes and complexes with the hIP. Furthermore, siRNA-disruption of
IKEPP
expression impaired hIP-induced endothelial cell migration and in vitro angiogenesis, revealing the functional importance of the
IKEPP
:IP interaction within the vascular endothelium. Identification of
IKEPP
as a functional interactant of the IP reveals novel mechanistic insights into the role of these proteins within the vasculature and, potentially, in other systems where they are co-expressed.
...
PMID:Interaction of the human prostacyclin receptor and the NHERF4 family member intestinal and kidney enriched PDZ protein (IKEPP). 2288 31
