The Structure and Function of P55^PIK Reveal a New Regulatory Subunit for Phosphatidylinositol 3-Kinase

Abstract

Phosphatidylinositol 3-kinase (PI-3 kinase) is implicated in the regulation of diverse cellular processes, including insulin-stimulated glucose transport. PI-3 kinase is composed of a 110-kDa catalytic subunit and an 85-kDa regulatory subunit. Here, we describe p55^PIK, a new regulatory subunit that was isolated by screening expression libraries with tyrosine-phosphorylated insulin receptor substrate 1 (IRS-1). p55^PIK is composed of a unique 30-residue NH₂ terminus followed by a proline-rich motif and two Src homology 2 (SH2) domains with significant sequence identify to those in p85. p55^PIK mRNA is expressed early during development, remains abundant in adult mouse brain and testis tissue, and is detectable in adult adipocytes and heart and kidney tissues. p55^PIK forms a stable complex with p110, and it associates with IRS-1 during insulin stimulation. Moreover, the activated insulin receptor phosphorylates p55^PIK in Sf9 cells, and insulin stimulates p55^PIK phosphorylation in CHO^IR/p55^PIK cells. The unique features of p55^PIK suggest that it is important in receptor signaling.