alpha(2)-Macroglobulin modulates the immunoregulatory function of the lipocalin placental protein 14

alpha(2)-Macroglobulin modulates the immunoregulatory function of the lipocalin placental protein 14

Riely G J; Rachmilewitz J; Koo P H; Tykocinski M L

Biochemical Journal

2000

2000-10

Human placental protein 14 (PP14; also known as glycodelin and progesterone-associatcd endometrial protein) is an immuno-suppressive protein of the lipocalin structural superfamily. Mechanisms regulating serum PP14's inmunosuppressive activity remain to be elucidated. In the present study, an interaction between PP14 and a major serum protein carrier, alpha (2)-macroglobulin (alpha M-2), was documented for the first time. Using native gel electrophoresis, we showed that PP14, as well as its alternative splice variant PP14.2, binds to both alpha M-2 and methylamine-activated (MA)-alpha M-2. Cross-competition studies demonstrated that the variants compete for binding to alpha M-2. PP14 bound to alpha M-2 and MA-alpha M-2 with K-d values of 167+/-70 and 221+/-56 nM (means+/-S.D.) respectively, as determined by surface plasmon resonance. Significantly, the addition of alpha M-2 or MA-alpha M-2 to a T-cell proliferation assay strongly potentiated the inhibitory capacity of PP14. On the basis of these findings, alpha M-2 emerges as the first serum protein that can physically associate with, and thereby regulate, PP14. Moreover, this represents the first documented interaction between the protein carrier alpha M-2 and a lipocalin protein.

alpha-2-macroglobulin; alpha-macroglobulin; binding; Biochemistry & Molecular Biology; factor-beta; glycodelin; human; immunosuppressive; inhibition; nerve growth-factor; phosphorylation; phytohemagglutinin; pregnancy proteins; proteins; receptor; serum carrier; serum transport; signal-transduction

Journal Article

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