PMID- 10026136
OWN - NLM
STAT- MEDLINE
DCOM- 19990318
LR  - 20190508
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 9
DP  - 1999 Feb 26
TI  - N-Linked glycosylation and sialylation of the acid-labile subunit. Role in
      complex formation with insulin-like growth factor (IGF)-binding protein-3 and the
      IGFs.
PG  - 5292-8
AB  - Over 75% of the circulating insulin-like growth factors (IGF-I and -II) are bound
      in 140-kDa ternary complexes with IGF-binding protein-3 (IGFBP-3) and the
      84-86-kDa acid-labile subunit (ALS), a glycoprotein containing 20 kDa of
      carbohydrate. The ternary complexes regulate IGF availability to the tissues.
      Since interactions of glycoproteins can be influenced by their glycan moieties,
      this study aimed to determine the role of ALS glycosylation in ternary complex
      formation. Complete deglycosylation abolished the ability of ALS to associate
      with IGFBP-3. To examine this further, seven recombinant ALS mutants each lacking
      one of the seven glycan attachment sites were expressed in CHO cells. All the
      mutants bound IGFBP-3, demonstrating that this interaction is not dependent on
      any single glycan chain. Enzymatic desialylation of ALS caused a shift in
      isoelectric point from 4.5 toward 7, demonstrating a substantial contribution of 
      anionic charge by sialic acid. Ionic interactions are known to be involved in the
      association between ALS and IGFBP-3. Desialylation reduced the affinity of ALS
      for IGFBP-3. IGF complexes by 50-80%. Since serum protein glycosylation is often 
      modified in disease states, the dependence of IGF ternary complex formation on
      the glycosylation state of ALS suggests a novel mechanism for regulation of IGF
      bioavailability.
FAU - Janosi, J B
AU  - Janosi JB
AD  - Kolling Institute of Medical Research, University of Sydney, Royal North Shore
      Hospital, St Leonards, New South Wales 2065, Australia.
FAU - Firth, S M
AU  - Firth SM
FAU - Bond, J J
AU  - Bond JJ
FAU - Baxter, R C
AU  - Baxter RC
FAU - Delhanty, P J
AU  - Delhanty PJ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Carrier Proteins)
RN  - 0 (DNA Primers)
RN  - 0 (Glycoproteins)
RN  - 0 (Insulin-Like Growth Factor Binding Protein 3)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Somatomedins)
RN  - 0 (insulin-like growth factor binding protein, acid labile subunit)
RN  - EC 3.2.1.- (Glycoside Hydrolases)
RN  - EC 3.2.1.- (endo-N-acetylneuraminidase)
RN  - EC 3.2.1.18 (Neuraminidase)
RN  - GZP2782OP0 (N-Acetylneuraminic Acid)
SB  - IM
MH  - Animals
MH  - Base Sequence
MH  - CHO Cells
MH  - Carrier Proteins/*metabolism
MH  - Cricetinae
MH  - DNA Primers
MH  - Glycoproteins/*metabolism
MH  - Glycoside Hydrolases/metabolism
MH  - Glycosylation
MH  - Insulin-Like Growth Factor Binding Protein 3/*metabolism
MH  - N-Acetylneuraminic Acid/*metabolism
MH  - Neuraminidase/metabolism
MH  - Protein Binding
MH  - Recombinant Proteins/metabolism
MH  - Somatomedins/*metabolism
EDAT- 1999/02/20 00:00
MHDA- 1999/02/20 00:01
CRDT- 1999/02/20 00:00
PHST- 1999/02/20 00:00 [pubmed]
PHST- 1999/02/20 00:01 [medline]
PHST- 1999/02/20 00:00 [entrez]
AID - 10.1074/jbc.274.9.5292 [doi]
PST - ppublish
SO  - J Biol Chem. 1999 Feb 26;274(9):5292-8. doi: 10.1074/jbc.274.9.5292.