The tyrosine kinase lck is critically involved in the growth transformation of human B lymphocytes.
Epstein-Barr virus (EBV) exposure of human B lymphocytes induces rapid, Ca(2+)-dependent tyrosine phosphorylation of two cytosolic proteins, one likely the CD21 EBV receptor and another unknown species of 55-60 kDa. We now identify the latter protein as the tyrosine kinase lck (p56lck). In T cells many activation events reduce the high constitutive p56lck expression levels typical for that lineage, and they induce the appearance of a 60-kDa lck species. We now demonstrate that in B cells exposed to EBV the at best low constitutive p56lck expression levels are rapidly and transiently up-regulated without generation of 60-kDa lck. lck-specific antisense oligonucleotides block p56lck induction and prevent subsequent B cell activation and immortalization whereas B cell activation by nononcogenic agents was unaffected. We propose that p56lck superinduction is a transformation prerequisite which signals entry into the oncogenic growth transformation process.
Cheung
R K
RK
Department of Pediatrics, University of Toronto, Ontario, Canada.
Dosch
H M
HM
D001402:B-Lymphocytes / Q000201:enzymology*; D001483:Base Sequence; D015153:Blotting, Western; D002472:Cell Transformation, Viral; D015870:Gene Expression; D004854:Herpesvirus 4, Human; D006801:Humans; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes / Q000737:chemistry; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D019000:Phosphotyrosine; D011505:Protein-Tyrosine Kinases / Q000502:physiology*; D013997:Time Factors; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
D015345:Oligonucleotide Probes; D016376:Oligonucleotides, Antisense; D019000:Phosphotyrosine; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck)