The Raf-1 serine-threonine kinase is a substrate for the p56lck protein tyrosine kinase in human T-cells.
The CD4 receptor subserves both adhesion and signal transduction functions on CD4+ T-lymphocytes. CD4 is physically associated with the src-related protein tyrosine kinase p56lck. Cell surface engagement of CD4 leads to enzymatic activation of the associated p56lck and the phosphorylation of T-cell proteins on tyrosine residues. We have identified a 72-74kD protein phosphorylated on tyrosine residues following activation of CD4-associated p56lck as the serine-threonine kinase Raf-1. The demonstration that Raf-1 is a substrate for the CD4/p56lck receptor system in normal cells suggests that receptor and nonreceptor classes of protein tyrosine kinases can independently engage functionally overlapping signal transduction pathways.
Thompson
P A
PA
Laboratory of Tumor Virus Biology, National Cancer Institute, Bethesda, Maryland 20892.
Ledbetter
J A
JA
Rapp
U R
UR
Bolen
J B
JB
D015496:CD4-Positive T-Lymphocytes / Q000201:enzymology*; D004789:Enzyme Activation / Q000502:physiology; D006801:Humans; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D008970:Molecular Weight; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D019908:Proto-Oncogene Proteins c-raf; D012016:Reference Values; D013379:Substrate Specificity
D011518:Proto-Oncogene Proteins; D011494:Protein Kinases; D011505:Protein-Tyrosine Kinases; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D019908:Proto-Oncogene Proteins c-raf