Structurally distinct membrane-associated and soluble forms of GH-binding protein in the mouse.
It has previously been shown that the large increase in GH-binding capacity of mouse liver microsomes during pregnancy is due largely to an increase in the amount of GH-binding protein (GHBP), with a more modest increase in GH receptor (GHR). Here we show that mouse liver GHBP is predominantly present as a membrane-associated protein structurally distinct from the soluble form of GHBP present in serum. Liver GHBP is associated with both intracellular membranes and the plasma membrane. Membrane-associated GHBP and soluble GHBP appear to be identical polypeptides distinguished by the addition of different N-glycans to asparagine residues. The pattern of release of GHBP from membranes by various treatments indicates that GHBP associates with membranes through noncovalent interactions with one or more membrane protein, but not with GHR. Covalent crosslinking provides evidence for several GHBP-associated membrane polypeptides, with molecular masses ranging from 58 kDa to over 200 kDa. These studies in the mouse and similar studies in the rat suggest that GHBP is an important cell-surface receptor for GH in the liver of these species. We postulate that an arginine-glycine-aspartic acid sequence found on rat and mouse GHBP but absent in other species is responsible for the association of GHBP with the plasma membrane by binding to one or more integrins on the surface of liver cells.
Cerio
R J
RJ
Biochemistry Program, Indiana University of Pennsylvania, 975 Oakland Avenue, Indiana, Pennsylvania 15705, USA.
Xing
F
F
Fatula
R J
RJ
Keith
D E
DE
Yang
X
X
Talamantes
F
F
Southard
J N
JN
Southard
J N
JN
D000818:Animals; D002352:Carrier Proteins / Q000032:analysis / Q000737:chemistry* / Q000378:metabolism; D002462:Cell Membrane / Q000737:chemistry; D003198:Computer Simulation; D003432:Cross-Linking Reagents; D005260:Female; D015151:Immunoblotting / Q000379:methods; D007425:Intracellular Membranes / Q000737:chemistry; D051379:Mice; D008862:Microsomes, Liver / Q000737:chemistry*; D008958:Models, Molecular; D011247:Pregnancy; D011485:Protein Binding
D002352:Carrier Proteins; D003432:Cross-Linking Reagents; C051815:somatotropin-binding protein