Differential trafficking of Src, Lyn, Yes and Fyn is specified by the state of palmitoylation in the SH4 domain.
Src-family tyrosine kinases (SFKs), which participate in a variety of signal transduction events, are known to localize to the cytoplasmic face of the plasma membrane through lipid modification. Recently, we showed that Lyn, an SFK member, is exocytosed to the plasma membrane via the Golgi region along the secretory pathway. We show here that SFK trafficking is specified by the palmitoylation state. Yes is also a monopalmitoylated SFK and is biosynthetically transported from the Golgi pool of caveolin to the plasma membrane. This pathway can be inhibited in the trans-Golgi network (TGN)-to-cell surface delivery by temperature block at 19 degrees C or dominant-negative Rab11 GTPase. A large fraction of Fyn, a dually palmitoylated SFK, is directly targeted to the plasma membrane irrespective of temperature block of TGN exit. Fyn(C6S), which lacks the second palmitoylation site, is able to traffic in the same way as Lyn and Yes. Moreover, construction of Yes(S6C) and chimeric Lyn or Yes with the Fyn N-terminus further substantiates the importance of the dual palmitoylation site for plasma membrane targeting. Taken together with our recent finding that Src, a nonpalmitoylated SFK, is rapidly exchanged between the plasma membrane and late endosomes/lysosomes, these results suggest that SFK trafficking is specified by the palmitoylation state in the SH4 domain.
Sato
Izumi
I
Department of Molecular Cell Biology, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba 260-8675, Japan.
Obata
Yuuki
Y
Kasahara
Kousuke
K
Nakayama
Yuji
Y
Fukumoto
Yasunori
Y
Yamasaki
Takahito
T
Yokoyama
Kazunari K
KK
Saito
Takashi
T
Yamaguchi
Naoto
N
D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D002462:Cell Membrane / Q000187:drug effects / Q000201:enzymology; D002522:Chlorocebus aethiops; D003513:Cycloheximide / Q000494:pharmacology; D003545:Cysteine / Q000378:metabolism; D005089:Exocytosis / Q000187:drug effects; D006801:Humans; D054878:Lipoylation / Q000187:drug effects; D008954:Models, Biological; D008969:Molecular Sequence Data; D009154:Mutation; D021381:Protein Transport / Q000187:drug effects; D051076:Proto-Oncogene Proteins c-fyn / Q000737:chemistry / Q000378:metabolism; D051575:Proto-Oncogene Proteins c-yes / Q000737:chemistry / Q000378:metabolism; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000737:chemistry / Q000378:metabolism; D013696:Temperature; D018909:src Homology Domains; D019061:src-Family Kinases / Q000737:chemistry* / Q000378:metabolism*; D021601:trans-Golgi Network / Q000187:drug effects / Q000201:enzymology
D003513:Cycloheximide; C494957:FYN protein, human; D051076:Proto-Oncogene Proteins c-fyn; D051575:Proto-Oncogene Proteins c-yes; D016392:Proto-Oncogene Proteins pp60(c-src); C489834:YES1 protein, human; C060902:lyn protein-tyrosine kinase; D019061:src-Family Kinases; D003545:Cysteine