PMID- 10446158
OWN - NLM
STAT- MEDLINE
DCOM- 19990909
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 34
DP  - 1999 Aug 20
TI  - Stromal cell-derived factor-1alpha associates with heparan sulfates through the
      first beta-strand of the chemokine.
PG  - 23916-25
AB  - Biological properties of chemokines are believed to be influenced by their
      association with glycosaminoglycans. Surface plasmon resonance kinetic analysis
      shows that the CXC chemokine stromal cell-derived factor-1alpha (SDF-1alpha),
      which binds the CXCR4 receptor, associates with heparin with an affinity constant
      of 38.4 nM (k(on) = 2.16 x 10(6) M(-1) s(-1) and k(off) = 0.083 x s(-1)). A
      modified SDF-1alpha (SDF-1 3/6) was generated by combined substitution of the
      basic cluster of residues Lys(24), His(25), and Lys(27) by Ser. SDF-1 3/6
      conserves the global native structure and functional properties of SDF-1alpha,
      but it is unable to interact with sensor chip-immobilized heparin. The biological
      relevance of these in vitro findings was investigated. SDF-1alpha was unable to
      bind in a CXCR4-independent manner on epithelial cells that were treated with
      heparan sulfate (HS)-degrading enzymes or constitutively lack HS expression. The 
      inability of SDF-1 3/6 to bind to cells underlines the importance of the
      identified basic cluster for the physiological interactions of SDF-1alpha with
      HS. Importantly, the amino-terminal domain of SDF-1alpha which is required for
      binding to, and activation of, CXCR4 remains exposed after binding to HS and is
      recognized by a neutralizing monoclonal antibody directed against the first
      residues of the chemokine. Overall, these findings indicate that the Lys(24),
      His(25), and Lys(27) cluster of residues forms, or is an essential part of, the
      HS-binding site which is distinct from that required for binding to, and
      signaling through, CXCR4.
FAU - Amara, A
AU  - Amara A
AD  - Unite d'Immunologie Virale, Institut Pasteur, 28 Rue du Dr. Roux, 75724 Paris
      Cedex 15, France.
FAU - Lorthioir, O
AU  - Lorthioir O
FAU - Valenzuela, A
AU  - Valenzuela A
FAU - Magerus, A
AU  - Magerus A
FAU - Thelen, M
AU  - Thelen M
FAU - Montes, M
AU  - Montes M
FAU - Virelizier, J L
AU  - Virelizier JL
FAU - Delepierre, M
AU  - Delepierre M
FAU - Baleux, F
AU  - Baleux F
FAU - Lortat-Jacob, H
AU  - Lortat-Jacob H
FAU - Arenzana-Seisdedos, F
AU  - Arenzana-Seisdedos F
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 (Chemokine CXCL12)
RN  - 0 (Chemokines, CXC)
RN  - 0 (Cxcl12 protein, mouse)
RN  - 0 (Glycosaminoglycans)
RN  - 0 (Receptors, CXCR4)
RN  - 9050-30-0 (Heparitin Sulfate)
SB  - IM
MH  - Animals
MH  - CHO Cells
MH  - Chemokine CXCL12
MH  - Chemokines, CXC/*metabolism
MH  - Cricetinae
MH  - Glycosaminoglycans/metabolism
MH  - Heparitin Sulfate/*metabolism
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Receptors, CXCR4/*physiology
EDAT- 1999/08/14 00:00
MHDA- 1999/08/14 00:01
CRDT- 1999/08/14 00:00
PHST- 1999/08/14 00:00 [pubmed]
PHST- 1999/08/14 00:01 [medline]
PHST- 1999/08/14 00:00 [entrez]
AID - 10.1074/jbc.274.34.23916 [doi]
AID - S0021-9258(19)55511-9 [pii]
PST - ppublish
SO  - J Biol Chem. 1999 Aug 20;274(34):23916-25. doi: 10.1074/jbc.274.34.23916.