Protein Phosphatase inhibitor 1: Proteins and Enzymes

The inhibitor of protein phosphatase 1 (IPP-1, I-1) is an endogenous inhibitor of protein phophastase 1 (PP-1), a signal transducer in many cellular pathways. IPP-1 is a member of heat-stable PP1 inhibitory subunits, which includes DARPP-32, (a homologue of IPP-1) and IPP-2. First discovered in rabbit skeletal muscle, IPP-1 is expressed in various mammalian tissues. IPP-1 inhibition of PP-1 is controlled through phosphorylation at Thr35 by cAMP-dependent protein kinase and a tetra-peptide consensus motif in various PP-1 binding proteins (1). IPP-1 is a hormonal control in muscle contraction, pituitary cell growth, synaptic plasticity by neurotransmitters, and glycogen metabolism (2). In vivo, IPP-1 is phosphorylated at Ser-67 by NCLK, which also initiates inhibition of PP-1 by IPP-1 (3). Triggered by increase in calcium level, IPP-1 is inactivated by PP2B through de-phosphorylation (4).