PMID- 10650937
OWN - NLM
STAT- MEDLINE
DCOM- 20000210
LR  - 20091119
IS  - 0013-7227 (Print)
IS  - 0013-7227 (Linking)
VI  - 141
IP  - 2
DP  - 2000 Feb
TI  - The effect of phosphorylation by casein kinase 2 on the activity of insulin-like 
      growth factor-binding protein-3.
PG  - 564-70
AB  - Insulin-like growth factor (IGF)-binding protein-3 (IGFBP-3) is known to be
      secreted as a phosphoprotein, constitutively phosphorylated at casein kinase 2
      (CK2) sites. To examine the effect of phosphorylation by CK2 on the properties of
      glycosylated human IGFBP-3, we phosphorylated plasma-derived IGFBP-3, containing 
      less than 1 mol/mol phosphoserine, in vitro. As judged by incorporated 32P,
      enzymatic deglycosylation did not decrease the phosphate content of
      phospho-IGFBP-3. Phosphorylation had no effect on IGF-I or IGF-II binding, but
      was inhibitory to acid-labile subunit binding in the presence of either IGF.
      Determined in simian virus 40-transformed human fibroblasts, cell association by 
      phospho-IGFBP-3 was inhibited approximately 50% compared with that of the
      nonphosphorylated preparation. Phospho-IGFBP-3 showed significant resistance to
      proteolysis by plasmin and a cysteine protease secreted by MCF-7 cells. However, 
      no difference was seen between the two preparations in their inhibition of
      IGF-I-stimulated DNA synthesis when coincubated with IGF-I in neonatal skin
      fibroblasts or MCF-7 breast cancer cells, and little difference was found in
      their ability to potentiate IGF-I-stimulated DNA synthesis when preincubated with
      fibroblasts. These results indicate that IGFBP-3 interaction with acid-labile
      subunit and with the cell surface, both of which involve basic carboxyl-terminal 
      residues, may be modulated by phosphorylation. Relative resistance to proteolysis
      and poor binding to cells suggest that CK2-phospho-IGFBP-3 may be a significant
      inhibitor of IGF activity in the extracellular environment.
FAU - Coverley, J A
AU  - Coverley JA
AD  - Kolling Institute of Medical Research, University of Sydney, Royal North Shore
      Hospital, St. Leonards, New South Wales, Australia.
FAU - Martin, J L
AU  - Martin JL
FAU - Baxter, R C
AU  - Baxter RC
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Endocrinology
JT  - Endocrinology
JID - 0375040
RN  - 0 (Insulin-Like Growth Factor Binding Protein 3)
RN  - 17885-08-4 (Phosphoserine)
RN  - 67763-96-6 (Insulin-Like Growth Factor I)
RN  - 67763-97-7 (Insulin-Like Growth Factor II)
RN  - EC 2.7.11.1 (Casein Kinase II)
RN  - EC 2.7.11.1 (Protein-Serine-Threonine Kinases)
SB  - AIM
SB  - IM
MH  - Casein Kinase II
MH  - Cells, Cultured
MH  - Fibroblasts/metabolism
MH  - Glycosylation
MH  - Humans
MH  - Insulin-Like Growth Factor Binding Protein 3/blood/*metabolism
MH  - Insulin-Like Growth Factor I/*metabolism
MH  - Insulin-Like Growth Factor II/*metabolism
MH  - Kinetics
MH  - Phosphorylation
MH  - Phosphoserine/analysis
MH  - Protein-Serine-Threonine Kinases/*metabolism
EDAT- 2000/01/29 00:00
MHDA- 2000/01/29 00:01
CRDT- 2000/01/29 00:00
PHST- 2000/01/29 00:00 [pubmed]
PHST- 2000/01/29 00:01 [medline]
PHST- 2000/01/29 00:00 [entrez]
AID - 10.1210/endo.141.2.7306 [doi]
PST - ppublish
SO  - Endocrinology. 2000 Feb;141(2):564-70. doi: 10.1210/endo.141.2.7306.