PMID- 10187864
OWN - NLM
STAT- MEDLINE
DCOM- 19990503
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 15
DP  - 1999 Apr 9
TI  - Cloning, characterization, and chromosomal location of a novel human K+-Cl-
      cotransporter.
PG  - 10661-7
AB  - Differential display polymerase chain reaction has been used to isolate genes
      regulated in vascular endothelial cells by the angiogenic factor vascular
      endothelial cell growth factor (VEGF). Analysis of one of the bands consistently 
      up-regulated by VEGF led us to the identification of a cDNA from a human
      umbilical vein endothelial cell library that is 77% identical to the human K+-Cl-
      cotransporter1 (KCC1). We have referred to the predicted protein as K+-Cl-
      cotransporter 3 (KCC3). Hydrophobicity analysis of the KCC3 amino acid sequence
      showed an almost identical pattern to KCC1, suggesting 12 membrane-spanning
      segments, a large extracellular loop with potential N-glycosylation sites, and
      cytoplasmic N- and C-terminal regions. The KCC3 mRNA was highly expressed in
      brain, heart, skeletal muscle, and kidney, showing a distinct pattern and size
      from KCC1 and KCC2. The KCC3 mRNA level in endothelial cells increased on
      treatment with VEGF and decreased with the proinflammatory cytokine tumor
      necrosis factor alpha, whereas KCC1 mRNA levels remained unchanged. Stable
      overexpression of KCC3 cDNA in HEK293 cells produced a glycoprotein of
      approximately 150 kDa, which was reduced to 120 kDa by glycosidase digestion. An 
      increased initial uptake rate of 86Rb was seen in clones with high KCC3
      expression, which was dependent on extracellular Cl- but not Na+ and was
      inhibitable by the loop diuretic agent furosemide. The KCC3 genomic localization 
      was shown to be 15q13 by fluorescence in situ hybridization. Radiation hybrid
      analysis placed KCC3 within an area associated with juvenile myoclonic epilepsy. 
      These results suggest KCC3 is a new member of the KCC family that is under
      distinct regulation from KCC1.
FAU - Hiki, K
AU  - Hiki K
AD  - Department of Human Immunology, Hanson Centre for Cancer Research, Institute of
      Medical and Veterinary Science and University of Adelaide, Adelaide, South
      Australia 5000.
FAU - D'Andrea, R J
AU  - D'Andrea RJ
FAU - Furze, J
AU  - Furze J
FAU - Crawford, J
AU  - Crawford J
FAU - Woollatt, E
AU  - Woollatt E
FAU - Sutherland, G R
AU  - Sutherland GR
FAU - Vadas, M A
AU  - Vadas MA
FAU - Gamble, J R
AU  - Gamble JR
LA  - eng
SI  - GENBANK/AF108831
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Carrier Proteins)
RN  - 0 (Chlorides)
RN  - 0 (DNA, Complementary)
RN  - 0 (RNA, Messenger)
RN  - 0 (Symporters)
RN  - 0 (potassium-chloride symporters)
RN  - RWP5GA015D (Potassium)
SB  - IM
MH  - Amino Acid Sequence
MH  - Carrier Proteins/*genetics/metabolism
MH  - Cells, Cultured
MH  - Chlorides/*metabolism
MH  - *Chromosomes, Human, Pair 15
MH  - Cloning, Molecular
MH  - DNA, Complementary/isolation & purification
MH  - Endothelium, Vascular/metabolism
MH  - Epilepsies, Myoclonic/genetics
MH  - Glycosylation
MH  - Humans
MH  - Molecular Sequence Data
MH  - Potassium/*metabolism
MH  - RNA, Messenger/metabolism
MH  - Sequence Alignment
MH  - *Symporters
EDAT- 1999/04/03 00:00
MHDA- 1999/04/03 00:01
CRDT- 1999/04/03 00:00
PHST- 1999/04/03 00:00 [pubmed]
PHST- 1999/04/03 00:01 [medline]
PHST- 1999/04/03 00:00 [entrez]
AID - 10.1074/jbc.274.15.10661 [doi]
AID - S0021-9258(19)73762-4 [pii]
PST - ppublish
SO  - J Biol Chem. 1999 Apr 9;274(15):10661-7. doi: 10.1074/jbc.274.15.10661.