v-Src and c-Src, nonpalmitoylated Src-family kinases, induce perinuclear accumulation of lysosomes through Rab7 in a kinase activity-independent manner.

Overexpression of the c-src proto-oncogene product with its increased kinase activity is observed in numerous cancer types. Oncogenic transformation is often associated with aberrant lysosome distribution. Here, we show that v-Src and c-Src, nonpalmitoylated Src kinases, largely localize to lysosomes and induce perinuclear accumulation of lysosomes through Rab7 in a manner dependent on the SH2 domain but dispensable for the kinase activity. Unlike v-Src and c-Src, the palmitoylated Src kinases c-Yes, Fyn and Lyn localize minimally to lysosomes and marginally affect lysosome distribution. These results suggest that elevated expression of nonpalmitoylated Src plays a critical role in lysosome distribution.