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.
Copyright 2001 Academic Press.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adaptor Proteins, Signal Transducing*
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Amino Acid Sequence
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Animals
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Base Sequence
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Cell Line
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Chromosome Mapping*
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Cloning, Molecular
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Crosses, Genetic
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Exons
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Female
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Humans
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Male
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Mice
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Mice, Inbred C57BL
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Molecular Sequence Data
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Multigene Family
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Muridae
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Nerve Tissue Proteins / chemistry
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Nerve Tissue Proteins / genetics*
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Nerve Tissue Proteins / metabolism
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Neuropeptides*
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Phosphotyrosine / metabolism
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Proteins / chemistry
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Proteins / genetics*
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Proteins / metabolism
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Rats
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Recombinant Proteins / metabolism
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Reverse Transcriptase Polymerase Chain Reaction
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Sequence Alignment
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Sequence Deletion
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Sequence Homology, Amino Acid
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Shc Signaling Adaptor Proteins
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Src Homology 2 Domain-Containing, Transforming Protein 1
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Src Homology 2 Domain-Containing, Transforming Protein 2
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Src Homology 2 Domain-Containing, Transforming Protein 3
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Transfection
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src Homology Domains
Substances
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Adaptor Proteins, Signal Transducing
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Nerve Tissue Proteins
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Neuropeptides
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Proteins
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Recombinant Proteins
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SHC1 protein, human
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SHC2 protein, human
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SHC3 protein, human
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Shc Signaling Adaptor Proteins
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Shc1 protein, mouse
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Shc1 protein, rat
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Shc2 protein, mouse
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Shc2 protein, rat
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Shc3 protein, mouse
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Shc3 protein, rat
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Src Homology 2 Domain-Containing, Transforming Protein 1
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Src Homology 2 Domain-Containing, Transforming Protein 2
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Src Homology 2 Domain-Containing, Transforming Protein 3
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Phosphotyrosine