CrkIII: a novel and biologically distinct member of the Crk family of adaptor proteins.
As the role for adaptor proteins constantly proliferates, appreciation of their importance has never been higher. The Crk family of adaptor proteins is no exception. Currently comprising four members, v-Crk, CrkI, CrkII and Crk-like protein, we have introduced a fifth member, CrkIII. Cloned by the CORT technique, CrkIII is identical in sequence to CrkII until the second of its two SH3 domains, which is disrupted partway through and results in a nonfunctional domain and a unique C-terminal sequence. We have demonstrated the existence of native CrkIII at the message level using RT-PCR and RNAse protection assays, and at the protein level in mouse fibroblasts. We show that CrkII overexpression is capable of enhancing insulin-stimulated ERK activity, whereas CrkIII is not, thus partially characterizing a novel member of the Crk family and elucidating important effects mediated by the c-terminal SH3 domain.
Prosser
Simon
S
Department of Medicine and Cardiovascular Research Center, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA.
Sorokina
Elena
E
Pratt
Phillip
P
Sorokin
Andrey
A
D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D003001:Cloning, Molecular; D005786:Gene Expression Regulation; D015723:Gene Library; D005822:Genetic Vectors / Q000235:genetics; D005920:Glomerular Mesangium / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D017921:Mastadenovirus / Q000235:genetics; D051379:Mice / Q000235:genetics*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D008969:Molecular Sequence Data; D005810:Multigene Family; D016297:Mutagenesis, Site-Directed; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D017434:Protein Structure, Tertiary; D011518:Proto-Oncogene Proteins / Q000737:chemistry / Q000235:genetics; D050737:Proto-Oncogene Proteins c-crk; D011993:Recombinant Fusion Proteins / Q000502:physiology; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014162:Transfection; D018909:src Homology Domains
D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; C476798:Crk protein, mouse; D007328:Insulin; D020033:Protein Isoforms; D011518:Proto-Oncogene Proteins; D050737:Proto-Oncogene Proteins c-crk; D011993:Recombinant Fusion Proteins; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases