Insulin-like growth factor-binding protein-5 (IGFBP-5) stimulates phosphorylation of the IGFBP-5 receptor.

The finding that insulin-like growth factor (IGF)-binding protein-5 (IGFBP-5) binding to mouse osteoblasts was capable of being downregulated by IGFBP-5 suggested that the 420-kDa membrane protein, which interacted with IGFBP-5, may be a signaling receptor (Andress, D. L. J. Biol. Chem. 270: 28289-28296, 1995). In the current study, a carboxy-terminal IGFBP-5 peptide, IGFBP-5-(201-218), which was found to competitively inhibit125I-IGFBP-5 binding and to specifically bind to osteoblast monolayers, was used to affinity-purify the 420-kDa membrane protein. Coincubation of the affinity-purified membrane protein with [32P]ATP resulted in autophosphorylation at serine residues. Serine phosphorylation of the 420-kDa protein was enhanced by intact IGFBP-5, IGFBP-5-(1-169), and IGFBP-5-(201-218). When the IGFBP-5 receptor was incubated with dephosphorylated casein in the presence of [32P]ATP, casein became phosphorylated on serine residues. These data indicate that IGFBP-5 stimulates the phosphorylation of the IGFBP-5 receptor and suggest that serine/threonine kinase activation may be important in mediating some of the IGF-independent effects of IGFBP-5.

[1]  C. Abrass,et al.  Heparin binding domain of insulin-like growth factor binding protein-5 stimulates mesangial cell migration. , 1997, American journal of physiology. Renal physiology.

[2]  P. Cohen,et al.  Insulin-like Growth Factor (IGF)-binding Protein-3 Induces Apoptosis and Mediates the Effects of Transforming Growth Factor-β1 on Programmed Cell Death through a p53- and IGF-independent Mechanism* , 1997, The Journal of Biological Chemistry.

[3]  C. Ohlsson,et al.  Growth hormone receptor activity is stimulated by insulin-like growth factor binding protein 5 in rat osteosarcoma cells. , 1996, Growth regulation.

[4]  D. Andress.  Heparin Modulates the Binding of Insulin-like Growth Factor (IGF) Binding Protein-5 to a Membrane Protein in Osteoblastic Cells (*) , 1995, The Journal of Biological Chemistry.

[5]  S. Mohan,et al.  Studies on the Mechanisms by Which Insulin-like Growth Factor (IGF) Binding Protein-4 (IGFBP-4) and IGFBP-5 Modulate IGF Actions in Bone Cells (*) , 1995, The Journal of Biological Chemistry.

[6]  K. Suzuki,et al.  Characterization of insulin-like growth factor-binding protein 5-degrading proteases produced throughout murine osteoblast differentiation. , 1995, Endocrinology.

[7]  D. Clemmons,et al.  Insulin-like growth factors and their binding proteins: biological actions. , 1995, Endocrine reviews.

[8]  R. Rosenfeld,et al.  Demonstration of receptors for insulin-like growth factor binding protein-3 on Hs578T human breast cancer cells. , 1993, The Journal of biological chemistry.

[9]  D. Clemmons,et al.  Insulin-like growth factor binding protein 1 stimulates cell migration and binds to the alpha 5 beta 1 integrin by means of its Arg-Gly-Asp sequence. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[10]  D. Andress,et al.  Carboxy-truncated insulin-like growth factor binding protein-5 stimulates mitogenesis in osteoblast-like cells. , 1993, Biochemical and biophysical research communications.

[11]  R. Rosenfeld,et al.  Insulin-like growth factor (IGF)-independent action of IGF-binding protein-3 in Hs578T human breast cancer cells. Cell surface binding and growth inhibition. , 1993, The Journal of biological chemistry.

[12]  D. Andress,et al.  Human osteoblast-derived insulin-like growth factor (IGF) binding protein-5 stimulates osteoblast mitogenesis and potentiates IGF action. , 1992, The Journal of biological chemistry.

[13]  S. S. Huang,et al.  Transforming growth factor beta (TGF-beta) type V receptor has a TGF-beta-stimulated serine/threonine-specific autophosphorylation activity. , 1992, The Journal of biological chemistry.

[14]  R. Weinberg,et al.  Expression cloning of the TGF-β type II receptor, a functional transmembrane serine/threonine kinase , 1992, Cell.

[15]  L. Mathews,et al.  Expression cloning of an activin receptor, a predicted transmembrane serine kinase , 1991, Cell.

[16]  D. Riddle,et al.  daf-1, a C. elegans gene controlling dauer larva development, encodes a novel receptor protein kinase , 1990, Cell.

[17]  M. Boes,et al.  Insulin-like growth factor-binding proteins from vascular endothelial cells: purification, characterization, and intrinsic biological activities. , 1989, Endocrinology.

[18]  G. M. Walton,et al.  Phosphorylation of high mobility group protein 14 by casein kinase II. , 1985, The Journal of biological chemistry.

[19]  P. Greengard,et al.  DARPP-32, a dopamine- and adenosine 3':5'-monophosphate-regulated neuronal phosphoprotein. II. Comparison of the kinetics of phosphorylation of DARPP-32 and phosphatase inhibitor 1. , 1984, The Journal of biological chemistry.

[20]  A. Cozzone,et al.  Chemical properties and separation of phosphoamino acids by thin-layer chromatography and/or electrophoresis. , 1991, Methods in enzymology.