Plasma transport of the 20,000-dalton variant of human growth hormone (20K): evidence for a 20K-specific binding site.
The 20,000-dalton variant of human GH (20K) is known to circulate in blood, but few details are known about its plasma transport. A substantial portion of 20K appears to be protein bound despite its low affinity for the receptor-related GH-binding protein (BP). We, therefore, investigated the binding pattern of 20K in human plasma. Radioiodinated 20K was incubated with plasma or plasma fractions, and the mixture was fractionated by gel filtration. Saturation/Scatchard analysis was performed with both 20K and 22,000-dalton GH (22K). The majority (approximately 80%) of protein-bound 20K was complexed with a low affinity BP (Ka = approximately 2 x 10(5) M-1), with the remainder complexed with the high affinity2 receptor-related BP. The binding of 20K to the low affinity BP was specific for 20K; it may involve a 20K-specific binding site on the previously described low affinity plasma BP (peak I) or a separate 20K-specific BP. 22K did not interact with this binding site/BP. Analysis of the 20K-BP complex by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and isoelectric focusing suggested, but did not prove, the existence of a separate BP for 20K. We conclude that 20K in plasma binds primarily to a low affinity, 20K-specific binding site (possibly a new, third GH-BP), with only a small fraction bound to the GH receptor-related BP. This binding pattern is markedly different from that of 22K, which is predominantly bound to the receptor-related BP. The existence of a 20K-specific binding site/BP suggests an as yet unrecognized role for this GH variant.
Baumann
G
G
Department of Medicine, Northwestern University Medical School, Chicago, Illinois 60611.
Shaw
M A
MA
D001345:Autoradiography; D001665:Binding Sites; D005075:Biological Evolution; D001692:Biological Transport; D002850:Chromatography, Gel; D013006:Growth Hormone / Q000097:blood* / Q000145:classification / Q000235:genetics; D006801:Humans; D007525:Isoelectric Focusing; D011956:Receptors, Cell Surface / Q000097:blood*; D017451:Receptors, Somatomedin
D011956:Receptors, Cell Surface; D017451:Receptors, Somatomedin; D013006:Growth Hormone