PMID- 10454575
OWN - NLM
STAT- MEDLINE
DCOM- 19990910
LR  - 20190508
IS  - 0270-7306 (Print)
IS  - 0270-7306 (Linking)
VI  - 19
IP  - 9
DP  - 1999 Sep
TI  - Insulin-induced phosphorylation and activation of cyclic nucleotide
      phosphodiesterase 3B by the serine-threonine kinase Akt.
PG  - 6286-96
AB  - Cyclic nucleotide phosphodiesterase (PDE) is an important regulator of the
      cellular concentrations of the second messengers cyclic AMP (cAMP) and cGMP.
      Insulin activates the 3B isoform of PDE in adipocytes in a phosphoinositide
      3-kinase-dependent manner; however, downstream effectors that mediate signaling
      to PDE3B remain unknown. Insulin-induced phosphorylation and activation of
      endogenous or recombinant PDE3B in 3T3-L1 adipocytes have now been shown to be
      inhibited by a dominant-negative mutant of the serine-threonine kinase Akt,
      suggesting that Akt is necessary for insulin-induced phosphorylation and
      activation of PDE3B. Serine-273 of mouse PDE3B is located within a motif (RXRXXS)
      that is preferentially phosphorylated by Akt. A mutant PDE3B in which serine-273 
      was replaced by alanine was not phosphorylated either in response to insulin in
      intact cells or by purified Akt in vitro. In contrast, PDE3B mutants in which
      alanine was substituted for either serine-296 or serine-421, each of which lies
      within a sequence (RRXS) preferentially phosphorylated by cAMP-dependent protein 
      kinase, were phosphorylated by Akt in vitro or in response to insulin in intact
      cells. Moreover, the serine-273 mutant of PDE3B was not activated by insulin when
      expressed in adipocytes. These results suggest that PDE3B is a physiological
      substrate of Akt and that Akt-mediated phosphorylation of PDE3B on serine-273 is 
      important for insulin-induced activation of PDE3B.
FAU - Kitamura, T
AU  - Kitamura T
AD  - Second Department of Internal Medicine, Kobe University School of Medicine,
      Chuo-ku, Kobe 650-0017, Japan.
FAU - Kitamura, Y
AU  - Kitamura Y
FAU - Kuroda, S
AU  - Kuroda S
FAU - Hino, Y
AU  - Hino Y
FAU - Ando, M
AU  - Ando M
FAU - Kotani, K
AU  - Kotani K
FAU - Konishi, H
AU  - Konishi H
FAU - Matsuzaki, H
AU  - Matsuzaki H
FAU - Kikkawa, U
AU  - Kikkawa U
FAU - Ogawa, W
AU  - Ogawa W
FAU - Kasuga, M
AU  - Kasuga M
LA  - eng
SI  - GENBANK/AJ132271
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Mol Cell Biol
JT  - Molecular and cellular biology
JID - 8109087
RN  - 0 (Insulin)
RN  - 0 (Isoenzymes)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Recombinant Proteins)
RN  - E0399OZS9N (Cyclic AMP)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.11.1 (Akt1 protein, rat)
RN  - EC 2.7.11.1 (Protein-Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.13 (Protein Kinase C)
RN  - EC 2.7.11.13 (protein kinase C lambda)
RN  - EC 3.1.4.17 (3',5'-Cyclic-AMP Phosphodiesterases)
RN  - EC 3.1.4.17 (Cyclic Nucleotide Phosphodiesterases, Type 3)
RN  - EC 3.1.4.17 (Pde3b protein, mouse)
RN  - EC 3.1.4.17 (Pde3b protein, rat)
SB  - IM
MH  - 3',5'-Cyclic-AMP Phosphodiesterases/genetics/*metabolism
MH  - 3T3 Cells
MH  - Amino Acid Sequence
MH  - Animals
MH  - CHO Cells
MH  - Cricetinae
MH  - Cyclic AMP/metabolism
MH  - Cyclic Nucleotide Phosphodiesterases, Type 3
MH  - Enzyme Activation
MH  - Insulin/*pharmacology
MH  - Isoenzymes
MH  - Mice
MH  - Molecular Sequence Data
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Phosphorylation
MH  - Point Mutation
MH  - Protein Kinase C/metabolism
MH  - Protein-Serine-Threonine Kinases/genetics/*metabolism
MH  - *Proto-Oncogene Proteins
MH  - Proto-Oncogene Proteins c-akt
MH  - Rats
MH  - Recombinant Proteins/genetics/metabolism
MH  - Sequence Homology, Amino Acid
PMC - PMC84592
EDAT- 1999/08/24 00:00
MHDA- 1999/08/24 00:01
CRDT- 1999/08/24 00:00
PHST- 1999/08/24 00:00 [pubmed]
PHST- 1999/08/24 00:01 [medline]
PHST- 1999/08/24 00:00 [entrez]
AID - 10.1128/mcb.19.9.6286 [doi]
PST - ppublish
SO  - Mol Cell Biol. 1999 Sep;19(9):6286-96. doi: 10.1128/mcb.19.9.6286.