A c-Cbl yeast two hybrid screen reveals interactions with 14-3-3 isoforms and cytoskeletal components.
The protein product of c-cbl proto-oncogene is known to interact with several proteins, including Grb2, Crk and PI3 kinase, and is thought to regulate signalling by many cell surface receptors. The precise function of c-Cbl in these pathways is not clear, although a genetic analysis in Caenorhabditis elegans suggests that c-Cbl is a negative regulator of the epidermal growth factor receptor. Here we describe a yeast two hybrid screen performed with c-Cbl in an attempt to further elucidate its role in signal transduction. The screen identified interactions involving c-Cbl and two 14-3-3 isoforms, cytokeratin 18, human unconventional myosin IC, and a recently identified SH3 domain containing protein, SH3 P17. We have used the yeast two hybrid assay to localise regions of c-Cbl required for its interaction with each of the proteins. Interaction with 14-3-3 is demonstrated in mammalian cell extracts.
Robertson
H
H
Trescowthick Research Laboratories, Peter MacCallum Cancer Institute, Victoria, Australia.
Langdon
W Y
WY
Thien
C B
CB
Bowtell
D D
DD
D048948:14-3-3 Proteins; D029742:Caenorhabditis elegans Proteins; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D019169:Jurkat Cells; D010446:Peptide Fragments / Q000235:genetics; D010449:Peptide Mapping; D011485:Protein Binding; D011506:Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D050721:Proto-Oncogene Proteins c-cbl; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D014170:Transformation, Genetic; D014446:Tyrosine 3-Monooxygenase; D044767:Ubiquitin-Protein Ligases
D048948:14-3-3 Proteins; D029742:Caenorhabditis elegans Proteins; D003598:Cytoskeletal Proteins; C000715470:MAS1 protein, human; D010446:Peptide Fragments; D011506:Proteins; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; C106207:par-5 protein, C elegans; D014446:Tyrosine 3-Monooxygenase; D050721:Proto-Oncogene Proteins c-cbl; D044767:Ubiquitin-Protein Ligases; C067419:CBL protein, human