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.
Kasahara
Kousuke
K
Department of Molecular Cell Biology, Graduate School of Pharmaceutical Sciences, Chiba University, Inohana, Chuo-ku, Chiba, Japan.
Nakayama
Yuji
Y
Yamaguchi
Naoto
N
D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D006367:HeLa Cells; D006801:Humans; D054878:Lipoylation; D008247:Lysosomes / Q000502:physiology*; D015688:Oncogene Protein pp60(v-src) / Q000378:metabolism*; D000090063:Proto-Oncogene Mas; D051076:Proto-Oncogene Proteins c-fyn / Q000378:metabolism; D051575:Proto-Oncogene Proteins c-yes / Q000378:metabolism; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000378:metabolism*; D020691:rab GTP-Binding Proteins / Q000378:metabolism*; D000090802:rab7 GTP-Binding Proteins; D019061:src-Family Kinases / Q000378:metabolism
C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D000090802:rab7 GTP-Binding Proteins; C000716463:rab7 GTP-binding proteins, human; D015688:Oncogene Protein pp60(v-src); D051076:Proto-Oncogene Proteins c-fyn; D051575:Proto-Oncogene Proteins c-yes; D016392:Proto-Oncogene Proteins pp60(c-src); C060902:lyn protein-tyrosine kinase; D019061:src-Family Kinases; D020691:rab GTP-Binding Proteins