A novel link between Lck, Bak expression and chemosensitivity.
Protein kinases are critically involved in signaling pathways that regulate cell growth, differentiation, activation, and survival. Lck, a member of the Src family of protein tyrosine kinases, plays a key role in T-lymphocyte activation and differentiation. However, under certain conditions Lck is also involved in the induction of apoptosis. In this issue of Oncogene, Samraj et al. used the Lck-defective JCaM1.6 cell line to demonstrate the critical role of Lck in the apoptotic response of T-cell leukemia cells to several chemotherapeutic drugs. They further showed that Lck controls the mitochondrial death pathway by regulating proapoptotic Bak expression. This chemosensitizing effect of Lck is independent of T-cell receptor signaling and does not require the kinase activity of Lck. These findings demonstrate that Lck might be part of two independent signaling pathways leading to either cell proliferation or apoptosis, and reveal a hitherto unrecognized link between Lck, Bak, and chemosensitivity of human leukemic cells.
Heyninck
K
K
Department for Molecular Biomedical Research, Unit of Molecular Signal Transduction in Inflammation, VIB, Ghent University, Technologiepark, B-9052, Gent, Belgium.
Beyaert
R
R
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007938:Leukemia / Q000188:drug therapy; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000096:biosynthesis* / Q000187:drug effects; D013601:T-Lymphocytes / Q000187:drug effects; D050998:bcl-2 Homologous Antagonist-Killer Protein / Q000096:biosynthesis* / Q000187:drug effects
D000970:Antineoplastic Agents; D050998:bcl-2 Homologous Antagonist-Killer Protein; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck)