Genomic organization of the Shc-related phosphotyrosine adapters and characterization of the full-length Sck/ShcB: specific association of p68-Sck/ShcB with pp135

Biochem Biophys Res Commun. 2001 Jun 22;284(4):1039-47. doi: 10.1006/bbrc.2001.5080.

Abstract

The Shc gene family is an emerging family, containing at least three members designated Shc/ShcA, Sck/Sli/ShcB, N-Shc/Rai/ShcC in mammals. In this study, we determined the genomic organization of the mouse Shc family. Coding regions of ShcA, B, and C each comprised 12 exons, spanned approximately 6, 20, and 65 kb, and located on chromosome 3, 10, and 13, respectively. Based on this genome analysis, we determined the full-length structure of mouse Sck/ShcB as a 68-kD protein. We found that the 68-kD full-length Sck/ShcB was more efficiently phosphorylated upon EGF treatment than the previously-analyzed CH2-deleted form. We also found that Sck specifically interacted with a 135-kD phosphoprotein (pp135) through its SH2 domain following membrane depolarization. The Sck-pp135 interaction was reduced by Src kinase inhibitors. These results suggest that Sck, but not N-Shc nor Shc, transmit signals in conjunction with pp135 following Src activation and/or calcium entry in the cell.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adaptor Proteins, Signal Transducing*
  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Cell Line
  • Chromosome Mapping*
  • Cloning, Molecular
  • Crosses, Genetic
  • Exons
  • Female
  • Humans
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Molecular Sequence Data
  • Multigene Family
  • Muridae
  • Nerve Tissue Proteins / chemistry
  • Nerve Tissue Proteins / genetics*
  • Nerve Tissue Proteins / metabolism
  • Neuropeptides*
  • Phosphotyrosine / metabolism
  • Proteins / chemistry
  • Proteins / genetics*
  • Proteins / metabolism
  • Rats
  • Recombinant Proteins / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sequence Alignment
  • Sequence Deletion
  • Sequence Homology, Amino Acid
  • Shc Signaling Adaptor Proteins
  • Src Homology 2 Domain-Containing, Transforming Protein 1
  • Src Homology 2 Domain-Containing, Transforming Protein 2
  • Src Homology 2 Domain-Containing, Transforming Protein 3
  • Transfection
  • src Homology Domains

Substances

  • Adaptor Proteins, Signal Transducing
  • Nerve Tissue Proteins
  • Neuropeptides
  • Proteins
  • Recombinant Proteins
  • SHC1 protein, human
  • SHC2 protein, human
  • SHC3 protein, human
  • Shc Signaling Adaptor Proteins
  • Shc1 protein, mouse
  • Shc1 protein, rat
  • Shc2 protein, mouse
  • Shc2 protein, rat
  • Shc3 protein, mouse
  • Shc3 protein, rat
  • Src Homology 2 Domain-Containing, Transforming Protein 1
  • Src Homology 2 Domain-Containing, Transforming Protein 2
  • Src Homology 2 Domain-Containing, Transforming Protein 3
  • Phosphotyrosine