Novel interaction partners of the TPR/MET tyrosine kinase.
A large variety of biological processes is mediated by stimulation of the receptor tyrosine kinase MET. Screening a mouse embryo cDNA library, we were able to identify several novel, putative intracellular TPR/MET-substrates: SNAPIN, DCOHM, VAV-1, Sorting nexin 2, Death associated protein kinase 3, SMC-1, Centromeric protein C, and hTID-1. Interactions as identified by yeast two-hybrid analysis were validated in vitro and in vivo by mammalian two-hybrid studies, a far-western assay and coimmunoprecipitation. Participation in apoptosis-regulating mechanisms through interaction with DAPK-3 and cell cycle control via binding to nuclear proteins such as CENPC and SMC-1 are possible new aspects of intracellular MET signaling.
Schaaf
Christian P
CP
Institute of Human Genetics, University Clinics of Heidelberg, Heidelberg, Germany.
Benzing
Jörg
J
Schmitt
Thomas
T
Erz
Dorothee H R
DH
Tewes
Magdalena
M
Bartram
Claus R
CR
Janssen
Johannes W G
JW
D000818:Animals; D015153:Blotting, Western / Q000379:methods; D004622:Embryo, Mammalian / Q000737:chemistry / Q000378:metabolism; D015723:Gene Library; D006801:Humans; D007668:Kidney / Q000166:cytology / Q000196:embryology; D051379:Mice; D016297:Mutagenesis, Site-Directed / Q000235:genetics; D015514:Oncogene Proteins, Fusion / Q000737:chemistry / Q000378:metabolism; D010455:Peptides; D011485:Protein Binding; D025941:Protein Interaction Mapping / Q000379:methods*; D011518:Proto-Oncogene Proteins / Q000737:chemistry* / Q000378:metabolism*; D019859:Proto-Oncogene Proteins c-met; D051381:Rats; D017978:Receptors, Growth Factor / Q000737:chemistry* / Q000378:metabolism*; D020539:Sequence Analysis, Protein / Q000379:methods; D013379:Substrate Specificity; D020798:Two-Hybrid System Techniques
D015514:Oncogene Proteins, Fusion; D010455:Peptides; D011518:Proto-Oncogene Proteins; D017978:Receptors, Growth Factor; C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met