A model phosphatase 2C -> phosphatase 1 activation cascade via dual control of inhibitor-1 (INH-1) and DARPP-32 dephosphorylation by two inositol glycan putative insulin mediators from beef liver

Two inositol phosphoglycans (IPG) isolated from beef liver and designated a s putative insulin mediators were demonstrated to reciprocally enhance the dephosphorylation of inhibitor-1 (INH-I) and DARPP-32, thus directly activa ting phosphatase 2C and disinhibiting phosphatase 1 in a potential protein phosphatase 2C --> phosphatase I cascade mechanism. One IPG termed pH 2.0, containing Dchiro-inositol and galactosamine, stimulated the dephosphorylat ion of INH-I and DARPP-32 in a dose-dependent manner in the low micromolar range. A second, termed pH 1.3, containing myo-inositol glucosamine and man nose acted reciprocally to inhibit the cAMP-dependent protein kinase phosph orylation of INH-I and DARPP-32 in a dose-dependent manner in the low micro molar range. These model experiments are discussed in terms of the observed dephosphorylation of INH-1 with insulin action documented in the literatur e and the activation of both phosphatase 1 and 2C described in intact cells and in vivo with insulin action. (C) 1999 Academic Press.