PMID- 10196204
OWN - NLM
STAT- MEDLINE
DCOM- 19990517
LR  - 20190508
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 16
DP  - 1999 Apr 16
TI  - Identification of the APS protein as a novel insulin receptor substrate.
PG  - 11186-93
AB  - In order to identify novel substrates involved in insulin receptor signaling, a
      yeast two-hybrid 3T3-L1 adipocyte cDNA library was screened with the cytoplasmic 
      domain of the human insulin receptor as bait. Here we describe the isolation and 
      characterization of an interacting protein, APS, which contains pleckstrin
      homology and Src homology 2 domains and several potential tyrosine
      phosphorylation sites. APS mRNA and protein are expressed primarily in skeletal
      muscle, heart, and adipose tissue, and in differentiated 3T3-L1 adipocytes. We
      show that APS associates with phosphotyrosines situated within the activation
      loop of the insulin receptor via the APS Src homology 2 domain. Insulin
      stimulation of 3T3-L1 adipocytes resulted in rapid tyrosine phosphorylation of
      endogenous APS on tyrosine 618, whereas platelet-derived growth factor treatment 
      resulted in no APS phosphorylation. In summary, we have identified a new insulin 
      receptor substrate that is primarily expressed in insulin-responsive tissues and 
      in 3T3-L1 adipocytes whose phosphorylation shows insulin receptor specificity.
      These findings suggest a potential role for APS in insulin-regulated metabolic
      signaling pathways.
FAU - Moodie, S A
AU  - Moodie SA
AD  - Metabolex, Inc., Hayward, California 94545, USA. smoodie@metabolex.com
FAU - Alleman-Sposeto, J
AU  - Alleman-Sposeto J
FAU - Gustafson, T A
AU  - Gustafson TA
LA  - eng
PT  - Journal Article
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Adaptor Proteins, Vesicular Transport)
RN  - 0 (DNA, Complementary)
RN  - 0 (IRS1 protein, human)
RN  - 0 (Insulin)
RN  - 0 (Insulin Receptor Substrate Proteins)
RN  - 0 (Irs1 protein, mouse)
RN  - 0 (Phosphoproteins)
RN  - 0 (Proteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (SH2B2 protein, human)
RN  - 0 (Sh2b2 protein, mouse)
RN  - 42HK56048U (Tyrosine)
RN  - EC 2.7.10.1 (Receptor, Insulin)
SB  - IM
MH  - 3T3 Cells
MH  - *Adaptor Proteins, Signal Transducing
MH  - *Adaptor Proteins, Vesicular Transport
MH  - Adipocytes/metabolism
MH  - Amino Acid Sequence
MH  - Animals
MH  - CHO Cells
MH  - Cloning, Molecular
MH  - Cricetinae
MH  - DNA, Complementary
MH  - Humans
MH  - Insulin/metabolism
MH  - Insulin Receptor Substrate Proteins
MH  - Mice
MH  - Molecular Sequence Data
MH  - Phosphoproteins/*metabolism
MH  - Phosphorylation
MH  - Proteins/genetics/*metabolism
MH  - RNA, Messenger/genetics/metabolism
MH  - Receptor, Insulin/metabolism
MH  - Sequence Homology, Amino Acid
MH  - Signal Transduction
MH  - Tyrosine/metabolism
MH  - src Homology Domains
EDAT- 1999/04/10 00:00
MHDA- 1999/04/10 00:01
CRDT- 1999/04/10 00:00
PHST- 1999/04/10 00:00 [pubmed]
PHST- 1999/04/10 00:01 [medline]
PHST- 1999/04/10 00:00 [entrez]
AID - 10.1074/jbc.274.16.11186 [doi]
PST - ppublish
SO  - J Biol Chem. 1999 Apr 16;274(16):11186-93. doi: 10.1074/jbc.274.16.11186.