7 point mutations were engineered and incorporated at the endogenous locus via homologous recombination of a targeting vector. Each mutation elicited a missense mutation, ablating tyrosine residues involved in Src, Grb2, PI3-K, RasGAP, SHP-2, and PLC-gamma signal transduction. Tyrosines at codons 578, 715, 739, 750, 770, and 1008 are substituted with phenylalanine, and a tyrosine at 1020 is substituted with isoleucine. A single FRT and loxP sites were left in introns 12 and 16, respectively.