IL-1 induces rapid phosphorylation of the IL-1 receptor.
The IL-1R on murine T cells is a Mr = 80,000 plasma membrane glycoprotein. cDNA cloning and transfection experiments have shown that this is an integral membrane protein, which binds both IL-1 alpha and IL-1 beta and transduces the IL-1 signal. A mAb, RM-5, which binds an epitope on the receptor which is distinct from the IL-1 binding site has been produced in rats. RM-5 has been used to immunoprecipitate the IL-1R from 32P-orthophosphate labeled CHO cells which express approximately 100,000 functional, murine rIL-1R/cell. Phosphorylation of the receptor was observed as early as 1 min after the addition of IL-1 and continued for periods of up to 30 min. Phosphorylation increases as the concentration of IL-1 increases from 10(-13) to 10(-8) M. Potassium hydroxide hydrolysis of the phosphorylated IL-1R shows that more than 90% of the phosphate is incorporated into serine or threonine. Thus, one of the earliest events after IL-1 binding to the IL-1R is activation of a serine/threonine protein kinase and phosphorylation of the IL-1R itself.
Gallis
B
B
Immunex Corporation, Seattle, WA 98101.
Prickett
K S
KS
Jackson
J
J
Slack
J
J
Schooley
K
K
Sims
J E
JE
Dower
S K
SK
D000818:Animals; D000911:Antibodies, Monoclonal / Q000032:analysis; D000918:Antibody Specificity; D001666:Binding Sites, Antibody; D002460:Cell Line; D004306:Dose-Response Relationship, Immunologic; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism / Q000494:pharmacology*; D007700:Kinetics; D010750:Phosphoproteins / Q000302:isolation & purification; D010766:Phosphorylation; D051381:Rats; D011971:Receptors, Immunologic / Q000096:biosynthesis / Q000378:metabolism*; D017472:Receptors, Interleukin-1
D000911:Antibodies, Monoclonal; D007375:Interleukin-1; D010750:Phosphoproteins; D011971:Receptors, Immunologic; D017472:Receptors, Interleukin-1