Identification and characterization of a novel cytoskeleton-associated pp60src substrate.
Transformation of cells by the src oncogene results in elevated tyrosine phosphorylation of two related proteins, p80 and p85 (p80/85). Immunostaining with specific monoclonal antibodies revealed a striking change of subcellular localization of p80/85 in src-transformed cells. p80/85 colocalizes with F-actin in peripheral extensions of normal cells and rosettes (podosomes) of src-transformed cells. Sequence analysis of cDNA clones encoding p80/85 revealed an amino-terminal domain composed of six copies of a direct tandem repeat, each repeat containing 37 amino acids, a carboxyl-terminal SH3 domain, and an interdomain region composed of a highly charged acidic region and a region rich in proline, serine, and threonine. The multidomain structure of p80/85 and its colocalization with F-actin in normal and src-transformed cells suggest that these proteins may associate with components of the cytoskeleton and contribute to organization of cell structure.
Wu
H
H
Department of Microbiology, Health Sciences Center, Charlottesville, Virginia 22908.
Reynolds
A B
AB
Kanner
S B
SB
Vines
R R
RR
Parsons
J T
JT
D000595:Amino Acid Sequence; D000818:Animals; D030161:Avian Proteins; D001483:Base Sequence; D015152:Blotting, Northern; D015153:Blotting, Western; D002472:Cell Transformation, Viral / Q000235:genetics / Q000502:physiology*; D002478:Cells, Cultured; D002642:Chick Embryo; D003001:Cloning, Molecular; D003598:Cytoskeletal Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D015688:Oncogene Protein pp60(v-src) / Q000378:metabolism*; D010766:Phosphorylation; D011487:Protein Conformation; D012091:Repetitive Sequences, Nucleic Acid / Q000235:genetics; D012694:Serine / Q000378:metabolism; D013912:Threonine / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism
D030161:Avian Proteins; D003598:Cytoskeletal Proteins; C071034:p80 protein, chicken; C071033:cytoskeletal p85 protein, chicken; D013912:Threonine; D014443:Tyrosine; D012694:Serine; D015688:Oncogene Protein pp60(v-src)