PMID- 10453981
OWN - NLM
STAT- MEDLINE
DCOM- 19990930
LR  - 20111117
IS  - 0001-527X (Print)
IS  - 0001-527X (Linking)
VI  - 46
IP  - 1
DP  - 1999
TI  - Differential regulation of signaling pathways for insulin and insulin-like growth
      factor I.
PG  - 51-60
AB  - The insulin receptor (IR) and the insulin-like growth factor receptor I (IGF-IR) 
      have different functions in cell growth, apoptosis, differentation, and
      transformation. Although some of these differences may be explained by the
      relative level of receptor expression and receptor structure (alpha and beta
      subunits), they may also be attributed to differences in intracellular signals
      generated by insulin and IGF-I. The presence of hybrid receptors (IR alphabeta
      subunits and IGF-IR alphabeta subunits) making up the heterotetramers has added a
      new dimension to our understanding of the functional roles of these receptors.
      However, to date the results of efforts to understand the differences between
      these two closely related receptors have indicated mostly similarities. For
      example, both receptors utilize IRS-1/IRS-2 and Shc as immediate downstream
      adaptors, leading to activation of the Ras, Raf, ERK kinases and PI-3 kinase
      pathways. We have used the yeast two hybrid system to identify proteins which
      bind to the activated IGF-IR but not to the IR. The cytoplasmic domain of the
      IGF-IR was used to screen a human fetal brain library and two isoforms of the
      14-3-3 family were identified. 14-3-3 proteins are a highly conserved family of
      proteins which have recently been shown to interact with other components of the 
      mitogenic and apoptotic signaling pathways, including Raf, BAD, Bcr/Bcr-Abl,
      middle-T antigen, Ksr, PKC, PI-3 kinase, ASK1 kinase, and cdc25C phosphatase. We 
      also identified human Grb10, an adaptor protein with SH2 domain associated with
      the IGF-IR beta subunit. Smith's laboratory showed that Grb10 preferentially
      binds to the IR in intact cells. Using the interaction trap screen (active
      cytoplasmic domain of the IGF-IR) 55PIK and SOCS-2 proteins were also identified.
      However, 55PIK and SOCS-2 also interact with the IR in the yeast two hybrid
      system. These studies raise the possibility that 14-3-3 and Grb10 may play a role
      in insulin and IGF-I signal transduction and may underlie the observed
      differences.
FAU - Lopaczynski, W
AU  - Lopaczynski W
AD  - Endocrinology Section, Metabolism Branch, National Cancer Institute, Bethesda,
      Maryland 20892-1374, USA. WLX@CU.NIH.GOV
LA  - eng
PT  - Journal Article
PT  - Review
PL  - Poland
TA  - Acta Biochim Pol
JT  - Acta biochimica Polonica
JID - 14520300R
RN  - 0 (Insulin)
RN  - 67763-96-6 (Insulin-Like Growth Factor I)
RN  - EC 2.7.10.1 (Receptor, IGF Type 1)
RN  - EC 2.7.10.1 (Receptor, Insulin)
SB  - IM
MH  - Humans
MH  - Insulin/*metabolism
MH  - Insulin-Like Growth Factor I/*metabolism
MH  - Protein Binding
MH  - Receptor, IGF Type 1/metabolism
MH  - Receptor, Insulin/metabolism
MH  - *Signal Transduction
RF  - 52
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]
PST - ppublish
SO  - Acta Biochim Pol. 1999;46(1):51-60.