MAGNESIUM PROTECTS PHOSPHATIDYLINOSITOL-4,5-BISPHOSPHATE-MEDIATED INACTIVATION OF CASEIN KINASE-I IN ERYTHROCYTE-MEMBRANE

Recent reports suggest that membrane-bound casein kinase I (MBCK I) activity in erythrocytes is inactivated by exogenously added phosphatidylinositol 4,5-bisphosphate (PIP2) (Bazenet et al. (1990) J. Biol. Chem. 265, 7369-7376; Brockman and Anderson (1991) J. Biol. Chem. 266, 2508-2512). Here we report that PIP2-mediated inhibition of MBCK I in erythrocytes is only observed if exogenous PIP2 and the kinase are allowed to interact in the absence of Mg2+. Prior incubation Of PIP2 with 1 mM Mg2+ prevents the inactivation of MBCK I by PIP2. Other divalent cations (Ni2+, Co2+, Mn2+, Cd2+, Ca2+) and trivalent metal ions (La3+, Cr3+, Al3+) did not protect MBCK I from PIP2-mediated inactivation, indicating that the protective effect is specific for Mg2+ only. We propose a role of Mg2+ in the interaction of CK I with phosphoinositides, and that PIP2-mediated inhibition of protein kinase(s) may be a non-physiological phenomenon.