The role of calpain in the selective increased phosphorylation of the anion-transport protein in red cell of hypertensive subjects.
The phosphorylation of the anion-transport protein (band 3) is selectively increased in human red cell membrane, following exposure of intact cells to ionophore and micromolar calcium. The phosphorylation is catalyzed by a membrane associated protein kinase distinct from either protein kinase C or Ca2+/calmodulin dependent protein kinase. We show that the increase in phosphorylation of band 3 is abolished if red cells had been pre-loaded with an inhibitor of calpain or with an anticalpain monoclonal antibody. Our findings suggest that calpain activity may control, both at a functional and at a structural level, the activity of this important transmembrane protein through the modulation of its susceptibility as a substrate of membrane bound protein kinase(s). Based on previous observations indicating the presence in erythrocytes from hypertensive patients of an uncontrolled intracellular calpain-mediated proteolytic system accompanied by an increased phosphorylation of band 3 protein(s), we suggest that our results may shed light on the type of molecular alteration which is associated with the hypertensive state.
Pontremoli
S
S
Institute of Biological Chemistry, University of Genoa, Italy.
Sparatore
B
B
Salamino
F
F
De Tullio
R
R
Pontremoli
R
R
Melloni
E
E
D027321:Anion Transport Proteins; D002154:Calpain / Q000037:antagonists & inhibitors / Q000502:physiology*; D002352:Carrier Proteins / Q000378:metabolism*; D002852:Chromatography, Ion Exchange; D004912:Erythrocytes / Q000201:enzymology / Q000378:metabolism*; D006801:Humans; D006973:Hypertension / Q000097:blood*; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism
D027321:Anion Transport Proteins; D002352:Carrier Proteins; D011494:Protein Kinases; D002154:Calpain