Figure 2.

Mutations of Lyn in genetically engineered mice.A) Deletion of exon 1 in Lyn^−/− mice. Schematic of the genomic region of Lyn highlighting the generation of Lyn^−/− mice through the replacement of exon one and surrounding sequences with a PGK-Neo cassette, transcribed in the opposite orientation to the Lyn gene. B) Lyn^up/up mice contain a point mutation of the C-terminal tyrosine, generating a phenylalanine (Y508F) that is unable to be phosphorylated. C) Lyn^Mld4/Mld4 mice contain a point mutation of a threonine at the end of the activation look, to a lysine (T410K), which inhibits the activity of the enzyme. D) WeeB mice contain a point mutation in the glycine loop, a glutamic acid is changed to a glycine (E260G), inhibiting binding of Mg-ATP, resulting in an inactive enzyme. E) The Tel-Lyn fusion juxtaposes the PNT domain of Tel (ETV6) with a truncated Lyn lacking its regulatory UN/SH3/SH2 domains, generating a constitutively active kinase fusion. Domains and motifs of Lyn are as described in Figure 1.