Genomic organization of the Shc-related phosphotyrosine adapters and characterization of the full-length Sck/ShcB: specific association of p68-Sck/ShcB with pp135.
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.
Kojima
T
T
Department of Molecular Genetic Research, National Institute for Longevity Sciences (NILS), Morioka-cho, Oobu, Aichi, 474-8522, Japan.
Yoshikawa
Y
Y
Takada
S
S
Sato
M
M
Nakamura
T
T
Takahashi
N
N
Copeland
N G
NG
Gilbert
D J
DJ
Jenkins
N A
NA
Mori
N
N
D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D003433:Crosses, Genetic; D005091:Exons; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D005810:Multigene Family; D009115:Muridae; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D009479:Neuropeptides; D019000:Phosphotyrosine / Q000378:metabolism; D011506:Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D051381:Rats; D011994:Recombinant Proteins / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016415:Sequence Alignment; D017384:Sequence Deletion; D017386:Sequence Homology, Amino Acid; D055765:Shc Signaling Adaptor Proteins; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; D000071426:Src Homology 2 Domain-Containing, Transforming Protein 2; D000071427:Src Homology 2 Domain-Containing, Transforming Protein 3; D014162:Transfection; D018909:src Homology Domains
D048868:Adaptor Proteins, Signal Transducing; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; D011506:Proteins; D011994:Recombinant Proteins; C528024:SHC1 protein, human; C099021:SHC2 protein, human; C122029:SHC3 protein, human; D055765:Shc Signaling Adaptor Proteins; C528034:Shc1 protein, mouse; C528035:Shc1 protein, rat; C486295:Shc2 protein, mouse; C486296:Shc2 protein, rat; C485682:Shc3 protein, mouse; C485683:Shc3 protein, rat; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; D000071426:Src Homology 2 Domain-Containing, Transforming Protein 2; D000071427:Src Homology 2 Domain-Containing, Transforming Protein 3; D019000:Phosphotyrosine