Phosphorylation of a Src kinase at the autophosphorylation site in the absence of Src kinase activity.
Exposure of cells to oxidants increases the phosphorylation of the Src family tyrosine protein kinase Lck at Tyr-394, a conserved residue in the activation loop of the catalytic domain. Kinase-deficient Lck expressed in fibroblasts that do not express any endogenous Lck has been shown to be phosphorylated at Tyr-394 following H(2)O(2) treatment to an extent indistinguishable from that seen with wild type Lck. This finding indicates that a kinase other than Lck itself is capable of phosphorylating Tyr-394. Because fibroblasts express other Src family members, it remained to be determined whether the phosphorylation of Tyr-394 was carried out by another Src family kinase or by an unrelated tyrosine protein kinase. We examined here whether Tyr-394 in kinase-deficient Lck was phosphorylated following exposure of cells devoid of endogenous Src family kinase activity to H(2)O(2). Strikingly, treatment of such cells with H(2)O(2) led to the phosphorylation of Tyr-394 to an extent identical to that seen with wild type Lck, demonstrating that Src family kinases are not required for H(2)O(2)-induced phosphorylation of Lck. Furthermore, this efficient phosphorylation of Lck at Tyr-394 in non-lymphoid cells suggests the existence of an ubiquitous activator of Src family kinases.
Chiang
G G
GG
Molecular Biology and Virology Laboratory, The Salk Institute for Biological Studies, La Jolla, California 92037, USA. gchiang@ucsd.edu
Sefton
B M
BM
D000818:Animals; D001665:Binding Sites; D002460:Cell Line; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000378:metabolism; D051379:Mice; D010449:Peptide Mapping; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000032:analysis; D014443:Tyrosine / Q000378:metabolism; D019061:src-Family Kinases / Q000378:metabolism*
D019000:Phosphotyrosine; D014443:Tyrosine; D006861:Hydrogen Peroxide; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D019061:src-Family Kinases