Insulin-Induced Phosphorylation and Activation of Cyclic Nucleotide Phosphodiesterase 3B by the Serine-Threonine Kinase Akt

• DOI: 10.1128/mcb.19.9.6286
• Publication Date: 2015-10-26T10:20:01Z
• Authors: Tadahiro Kitamura; Yukari Kitamura; Shoji Kuroda; Yasuhisa Hino; Miwa Ando; Ko Kotani; Hiroaki Konishi; Hidenori Matsuzaki; Ushio Kikkawa; Wataru Ogawa; Masato Kasuga
• Keywords: Proto-Oncogene Proteins c-akt; AKT3; AKT2

Cyclic nucleotide phosphodiesterase (PDE) is an important regulator of the cellular concentrations second messengers cyclic AMP (cAMP) and cGMP. Insulin activates 3B isoform PDE in adipocytes a phosphoinositide 3-kinase-dependent manner; however, downstream effectors that mediate signaling to PDE3B remain unknown. Insulin-induced phosphorylation activation endogenous or recombinant 3T3-L1 have now been shown be inhibited by dominant-negative mutant serine-threonine kinase Akt, suggesting Akt necessary for insulin-induced PDE3B. Serine-273 mouse located within motif (RXRXXS) preferentially phosphorylated Akt. A which serine-273 was replaced alanine not either response insulin intact cells purified vitro. In contrast, mutants substituted serine-296 serine-421, each lies sequence (RRXS) cAMP-dependent protein kinase, were vitro cells. Moreover, activated when expressed adipocytes. These results suggest physiological substrate Akt-mediated on