Interaction of the c-cbl proto-oncogene product with the Tyk-2 protein tyrosine kinase.
The c-cbl proto-oncogene product (p120cbl) forms a stable complex with the Tyk-2 protein tyrosine kinase in various human cell lines of diverse hematopoietic origin. In U-266 myeloma and 293T embryonic kidney cells, p120cbl is rapidly phosphorylated on tyrosine in an IFN alpha-dependent manner. p120cbl also acts as a specific substrate for the Tyk-2-associated SHP-1 phosphatase in vitro, suggesting that this phosphatase plays a regulatory role on the phosphorylation of the protein. These data provide evidence that p120cbl interacts with the functional Type I IFN receptor complex, and suggest its involvement in IFN alpha signaling.
Uddin
S
S
Division of Hematology-Oncology, Loyola University Chicago, Maywood, Illinois 60153, USA.
Gardziola
C
C
Dangat
A
A
Yi
T
T
Platanias
L C
LC
D002460:Cell Line; D006801:Humans; D016898:Interferon-alpha / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins; D010766:Phosphorylation; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism*; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D050721:Proto-Oncogene Proteins c-cbl; D053633:Receptor, Interferon alpha-beta; D017471:Receptors, Interferon / Q000378:metabolism; D015398:Signal Transduction; D013379:Substrate Specificity; D053634:TYK2 Kinase; D044767:Ubiquitin-Protein Ligases
D016898:Interferon-alpha; D047908:Intracellular Signaling Peptides and Proteins; C000715470:MAS1 protein, human; D011506:Proteins; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D017471:Receptors, Interferon; D053633:Receptor, Interferon alpha-beta; D050721:Proto-Oncogene Proteins c-cbl; D044767:Ubiquitin-Protein Ligases; D011505:Protein-Tyrosine Kinases; D053634:TYK2 Kinase; C070139:TYK2 protein, human; C516724:PTPN11 protein, human; C509249:PTPN6 protein, human; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases; C067419:CBL protein, human