Targeting of Proteins to Membranes by Fatty Acylation
Membrane targeting of Src family kinases
We are investigating the role of myristate and palmitate in targeting proteins to membranes and to plasma membrane microdomains known as rafts. Our focus is on the Src family of protein tyrosine kinases. We have stablished that Src kinases, as well as other fatty acylated proteins, use a “two signal” mechanism for membrane association: myristate + basic (a cluster of basic residues near the N-terminus) or myristate + palmitate.
We are currently studying how c-Src moves throughout the cell, specifically into and out of endosomes and the plasma membrane. High resolution microscopy techniques are being applied to live imaging in order to monitor protein trafficking in real time.
Liang X, Lu Y, Wilkes M, Neubert TA, Resh MD. Related Articles, Links The N-terminal SH4 region of the Src family kinase Fyn is modified by methylation and heterogeneous fatty acylation: role in membrane targeting, cell adhesion, and spreading. J Biol Chem. 2004 Feb 27;279(9):8133-9.
van’t Hof W, Resh MD. 1999 Dual fatty acylation of p59(Fyn) is required for association with the T cell receptor zeta chain through phosphotyrosine-Src homology domain-2 interactions. J Cell Biol. 1999;145:377-389.
van’t Hof W, Resh MD. 1997 Rapid plasma membrane anchoring of newly synthesized p59fyn: selective requirement for NH2-terminal myristoylation and palmitoylation at cysteine-3. J Cell Biol. 1997 Mar 10;136(5):1023-35.
Liang X, Nazarian A, Erdjument-Bromage H, Bornmann W, Tempst P, Resh MD. 2001 Heterogeneous fatty acylation of Src family kinases with polyunsaturated fatty acids regulates raft localization and signal transduction. J Biol Chem. 2001;276:30987-30994.