TI  - Protein binding and signaling properties of <prot>RIN1</prot> suggest a unique effector
      function.
PG  - 4954-9
AB  - Human <prot>RIN1</prot> was first characterized as a <prot><prot>RAS</prot> binding protein</prot> based on the
      properties of its carboxyl-terminal domain. We now show that full-length
       <prot>RIN1</prot>  interacts with activated  <prot>RAS</prot>  in mammalian cells and defines a minimum
      region of 434 aa required for efficient <prot>RAS</prot> binding.  <prot>RIN1</prot>  interacts with
      the &quot;effector domain&quot; of  <prot>RAS</prot>  and employs some <prot>RAS</prot> determinants that are
      common to, and others that are distinct from, those required for the
      binding of <prot>RAF1</prot>, a known <prot>RAS</prot> effector. The same domain of   <prot>RIN1</prot>   that binds
       <prot>RAS</prot>  also interacts with  14-3-3 proteins , extending the similarity between
      <prot>RIN1</prot> and other <prot>RAS</prot> effectors. When expressed in mammalian cells, the  <prot>RAS</prot> 
      binding domain of  <prot>RIN1</prot>  can act as a dominant negative signal transduction
      blocker. The amino-terminal domain of <prot>RIN1</prot> contains a proline-rich
      sequence similar to consensus Src homology 3 (SH3) binding regions. This
       <prot>RIN1</prot>  sequence shows preferential binding to the  <prot>ABL-SH3</prot>  domain in vitro.
      Moreover, the amino-terminal domain of  <prot>RIN1</prot>  directly associates with, and
      is tyrosine phosphorylated by,  <prot>c-ABL</prot> . In addition, <prot>RIN1</prot> encodes a
      functional SH2 domain that has the potential to activate downstream
      signals. These data suggest that <prot>RIN1</prot> is able to mediate multiple signals.
      A differential pattern of expression and alternate splicing indicate
      several levels of <prot>RIN1</prot> regulation.
AD  - Department of Biological Chemistry, Molecular Genetics, and Immunology,
