Interleukin-8 receptor beta. The role of the carboxyl terminus in signal transduction.
Two interleukin-8 (IL-8) receptors, alpha and beta, have been identified and cloned. Both receptors are thought to transduce signals by coupling to GTP-binding proteins. The aim of this study is to determine whether the carboxyl terminus (C') of IL-8 receptor beta (IL-8R beta) is involved in signaling in response to IL-8. We have constructed a number of IL-8R beta genes that encode truncated forms of the IL-8R beta. The deletions consisted of amino acids 349-355, 336-355, 325-355, and 317-355 (termed beta 2, beta 3, beta 4, and beta 5, respectively). 293 human embryonic kidney cells were transfected with the wild type IL-8R beta (beta 1) and with these mutants. Cells transfected with the mutated receptors expressed the receptors and bound IL-8 with the same high affinity as cells transfected with the wild type receptor. The capacity of the mutated receptors to convey functional signals was evaluated by comparing the chemotaxis index of cells expressing the C'-truncated receptors to the index of cells expressing the wild type receptor. The results indicate that while cells expressing beta 1, beta 2, beta 3, and beta 4 were chemoattracted in response to IL-8, cells expressing beta 5 did not migrate in response to IL-8 stimulation. Therefore, the data suggest that amino acids 317-324 are involved in signaling by IL-8R beta.
Ben-Baruch
A
A
Laboratory of Molecular Immunoregulation, Frederick Cancer Research and Development Center, Maryland, USA.
Bengali
K M
KM
Biragyn
A
A
Johnston
J J
JJ
Wang
J M
JM
Kim
J
J
Chuntharapai
A
A
Michiel
D F
DF
Oppenheim
J J
JJ
Kelvin
D J
DJ
D002633:Chemotaxis; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism*; D009154:Mutation; D018123:Receptors, Interleukin / Q000737:chemistry / Q000502:physiology*; D023062:Receptors, Interleukin-8A; D015398:Signal Transduction; D013329:Structure-Activity Relationship; D014162:Transfection
D016209:Interleukin-8; D018123:Receptors, Interleukin; D023062:Receptors, Interleukin-8A