Lipid segregation and IgE receptor signaling: a decade of progress.
Recent work to characterize the roles of lipid segregation in IgE receptor signaling has revealed a mechanism by which segregation of liquid ordered regions from disordered regions of the plasma membrane results in protection of the Src family kinase Lyn from inactivating dephosphorylation by a transmembrane tyrosine phosphatase. Antigen-mediated crosslinking of IgE receptors drives their association with the liquid ordered regions, commonly called lipid rafts, and this facilitates receptor phosphorylation by active Lyn in the raft environment. Previous work showed that the membrane skeleton coupled to F-actin regulates stimulated receptor phosphorylation and downstream signaling processes, and more recent work implicates cytoskeletal interactions with ordered lipid rafts in this regulation. These and other results provide an emerging view of the complex role of membrane structure in orchestrating signal transduction mediated by immune and other cell surface receptors.
Holowka
David
D
Department of Chemistry and Chemical Biology, Cornell University, Baker Laboratory, Ithaca, NY 14853-1301, USA.
Gosse
Julie A
JA
Hammond
Adam T
AT
Han
Xuemei
X
Sengupta
Prabuddha
P
Smith
Norah L
NL
Wagenknecht-Wiesner
Alice
A
Wu
Min
M
Young
Ryan M
RM
Baird
Barbara
B
D000818:Animals; D002462:Cell Membrane / Q000378:metabolism*; D003599:Cytoskeleton / Q000502:physiology; D006801:Humans; D008563:Membrane Lipids / Q000502:physiology*; D021962:Membrane Microdomains / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D010766:Phosphorylation; D017455:Receptors, IgE / Q000502:physiology*; D015398:Signal Transduction; D019061:src-Family Kinases / Q000378:metabolism*
D008563:Membrane Lipids; D008565:Membrane Proteins; D017455:Receptors, IgE; C060902:lyn protein-tyrosine kinase; D019061:src-Family Kinases