TI  - Evidence for a differential interaction of <prot>SHC</prot> and the  <prot>insulin receptor
      substrate-1</prot> (<prot>IRS-1</prot>)  with the  <prot><prot>insulin-like growth factor-I</prot> (<prot>IGF-I</prot>)  receptor</prot>
      in the yeast two-hybrid system.
PG  - 23456-60
AB  - Using the yeast two-hybrid system, a genetic assay for studying
      protein-protein interactions, we have examined and compared the
      interaction of the   <prot><prot>insulin-like growth factor-I</prot> receptor</prot> (<prot>IGF-IR</prot>)   and the
        <prot>insulin receptor</prot> (<prot>IR</prot>)   with their two known substrates   <prot>p52Shc</prot>   and the
        <prot><prot>insulin receptor</prot> substrate-1</prot> (<prot>IRS-1</prot>)  . We also mapped the specific domains
      of the <prot>IGF-IR</prot> and <prot>p52Shc</prot> participating in these interactions. Our findings
      can be summarized as follows: (i) the tyrosine kinase activity of the
        <prot>IGF-IR</prot>   is essential for the interaction with  <prot>p52Shc</prot>  and  <prot>IRS-1</prot> , (ii)  <prot>p52Shc</prot> 
      and  <prot>IRS-1</prot>  bind to the   <prot>IGF-IR</prot>   in the NPEY-juxtamembrane motif, (iii)
      contrary to <prot>p52Shc</prot>,  <prot>IRS-1</prot>  binds also to the major autophosphorylation
      sites (Tyr-1131, -1135, and -1136) of the  <prot>IGF-IR</prot> , and (iv) the
      amino-terminal domain of    <prot>p52Shc</prot>   is required for its association with the
       <prot>IR</prot>  and the  <prot>IGF-IR</prot> . We propose that (i) the <prot>IGF-IR</prot> and the <prot>IR</prot> share at
      least in part the same molecular mechanism underlying their interplay with
      their two substrates, <prot>p52Shc</prot> and <prot>IRS-1</prot>, and (ii)  <prot>IRS-1</prot>  interacts with the
        <prot>IGF-IR</prot>   in a fashion that is different from that used by  <prot>p52Shc</prot> . Finally,
      our data highlight the crucial role of the juxtamembrane domain in
      signaling by both the <prot>IR</prot> and the <prot>IGF-IR</prot>.
AD  - INSERM U145, Nice, France.
