title: Structure-function analysis of nucleolin and ErbB receptors interactions.
abstract: BACKGROUND
  The ErbB receptor tyrosine kinases and nucleolin are major contributors to malignant transformation. Recently we have found that cell-surface ErbB receptors interact with nucleolin via their cytoplasmic tail. Overexpression of ErbB1 and nucleolin leads to receptor phosphorylation, dimerization and anchorage independent growth.
  
  
  RESULTS
  In the present study we explored the regions of nucleolin and ErbB responsible for their interaction. Using mutational analyses, we addressed the structure-function relationship of the interaction between ErbB1 and nucleolin. We identified the ErbB1 nuclear localization domain as nucleolin interacting region. This region is important for nucleolin-associated receptor activation. Notably, though the tyrosine kinase domain is important for nucleolin-associated receptor activation, it is not involved in nucleolin/ErbB interactions. In addition, we demonstrated that the 212 c-terminal portion of nucleolin is imperative for the interaction with ErbB1 and ErbB4. This region of nucleolin is sufficient to induce ErbB1 dimerization, phosphorylation and growth in soft agar.
  
  
  CONCLUSIONS
  The oncogenic potential of ErbB depends on receptor levels and activation. Nucleolin affects ErbB dimerization and activation leading to enhanced cell growth. The C-terminal region of nucleolin and the ErbB1 NLS-domain mediate this interaction. Moreover, when the C-terminal 212 amino acids region of nucleolin is expressed with ErbB1, it can enhance anchorage independent cell growth. Taken together these results offer new insight into the role of ErbB1 and nucleolin interaction in malignant cells.
authors: Department of Neurobiology, Tel-Aviv University, Ramat-Aviv, Israel.
authors: Keren
authors: K
authors: Farin
authors: Ayelet
authors: A
authors: Di Segni
authors: Adam
authors: A
authors: Mor
authors: Ronit
authors: R
authors: Pinkas-Kramarski
mesh_terms: D001483:Base Sequence; D002460:Cell Line; D017931:DNA Primers; D066246:ErbB Receptors / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D010750:Phosphoproteins / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D011485:Protein Binding; D016601:RNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D013329:Structure-Activity Relationship; D000097796:Nucleolin
chemical_list: D017931:DNA Primers; D066246:ErbB Receptors; D010750:Phosphoproteins; D016601:RNA-Binding Proteins; D000097796:Nucleolin; C512478:EGFR protein, human