Erythroid membrane-bound protein kinase binds to a membrane component and is regulated by phosphatidylinositol 4,5-bisphosphate.
In the erythrocyte, a membrane-bound serine/threonine protein kinase (a casein kinase) has been shown to phosphorylate a number of membrane proteins, modulating their function. Here we report that the membrane-bound protein kinase binds to membranes by an association with a minor membrane component contained in preparations of glycophorin (possibly a minor glycophorin). The binding of the kinase to glycophorins does not significantly modify kinase activity. However, upon binding, the kinase activity is potently inhibited by phosphatidylinositol 4,5-bisphosphate, and the affinity of the kinase for the glycophorins is increased. Other phospholipids or polyanions such as inositol 1,4,5-trisphosphate or 2,3-diphosphoglycerate do not affect protein kinase activity when the kinase is bound to membranes but do inhibit the solubilized membrane-bound kinase. In the erythrocyte, there is a cytosolic form of the casein kinase which is very similar, having the same molecular weight and substrate specificity as the membrane-bound casein kinase. The cytosolic casein kinase is inhibited by 2,3-diphosphoglycerate but much less so by glycophorin preparations containing phosphoinositol 4,5-bisphosphate. When the sequences of both casein kinases were compared by two-dimensional peptide mapping, it was found that the two kinases were very similar but not identical.
Bazenet
C E
CE
Department of Pharmacology, University of Wisconsin Medical School, Madison 53706.
Brockman
J L
JL
Lewis
D
D
Chan
C
C
Anderson
R A
RA
D047388:Casein Kinases; D002846:Chromatography, Affinity; D003600:Cytosol / Q000201:enzymology; D004910:Erythrocyte Membrane / Q000201:enzymology*; D004912:Erythrocytes / Q000201:enzymology; D006021:Glycophorins / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D008081:Liposomes; D008823:Micelles; D010449:Peptide Mapping; D019269:Phosphatidylinositol 4,5-Diphosphate; D010716:Phosphatidylinositols / Q000097:blood / Q000494:pharmacology*; D010743:Phospholipids / Q000494:pharmacology; D011485:Protein Binding; D011494:Protein Kinases / Q000097:blood* / Q000302:isolation & purification
D006021:Glycophorins; D008081:Liposomes; D008823:Micelles; D019269:Phosphatidylinositol 4,5-Diphosphate; D010716:Phosphatidylinositols; D010743:Phospholipids; D011494:Protein Kinases; D047388:Casein Kinases