TI  - Two potentially oncogenic cyclins,  <prot>cyclin A</prot>  and  <prot>cyclin D1</prot> , share common
      properties of subunit configuration, tyrosine phosphorylation and physical
      association with the   <prot>Rb</prot> protein  
PG  - 1377-84
AB  - Originally identified as a 'mitotic cyclin', <prot>cyclin A</prot> exhibits properties
      of growth factor sensitivity, susceptibility to viral subversion and
      association with a tumor-suppressor protein, properties which are
      indicative of an <prot>S-phase-promoting factor</prot> (<prot>SPF</prot>) as well as a candidate
      proto-oncogene. Other recent studies have identified human <prot>cyclin D1</prot>
      (<prot>PRAD1</prot>) as a putative G1 cyclin and candidate proto-oncogene. However, the
      specific enzymatic activities and, hence, the precise biochemical
      mechanisms through which cyclins function to govern cell cycle progression
      remain unresolved. In the present study we have investigated the
      coordinate interactions between these two potentially oncogenic cyclins,
      cyclin-dependent protein kinase subunits (cdks) and the <prot>Rb</prot>
      tumor-suppressor protein. The distribution of <prot>cyclin D</prot> isoforms was
      modulated by serum factors in primary fetal rat lung epithelial cells.
      Moreover,  <prot>cyclin D1</prot>  was found to be phosphorylated on tyrosine residues in
      vivo and, like  <prot>cyclin A</prot> , was readily phosphorylated by   <prot>pp60c-src</prot>   in vitro.
      In synchronized human osteosarcoma cells,  <prot>cyclin D1</prot>  is induced in early G1
      and becomes associated with  <prot>p9Ckshs1</prot> , a Cdk-binding subunit.
      Immunoprecipitation experiments with human osteosarcoma cells and Ewing's
      sarcoma cells demonstrated that   <prot>cyclin D1</prot>   is associated with both  <prot>p34cdc2</prot> 
      and  <prot>p33cdk2</prot> , and that <prot>cyclin D1</prot> immune complexes exhibit appreciable
      histone H1 kinase activity. Immobilized, recombinant  cyclins A  and  D1  were
      found to associate with cellular proteins in complexes that contain the
        <prot>p105Rb</prot>   protein. This study identifies several common aspects of cyclin
      biochemistry, including tyrosine phosphorylation and the potential to
      interact directly or indirectly with the <prot>Rb</prot> protein, that may ultimately
      relate membrane-mediated signaling events to the regulation of gene
      expression.
AD  - Division of Orthopaedic Surgery, Children's Hospital Los Angeles,
