Identification of a unique filamin A binding region within the cytoplasmic domain of glycoprotein Ibα

被引:35
作者
Cranmer, SL
Pikovski, I
Mangin, P
Thompson, PE
Domagala, T
Frazzetto, M
Salem, HH
Jackson, SP
机构
[1] Monash Univ, Australian Ctr Blood Dis, Prahran, Vic 3181, Australia
[2] Monash Univ, Victorian Coll Pharm, Dept Med Chem, Parkville, Vic 3052, Australia
关键词
adhesion receptor; cytoplasmic domain; filamin A; GPIb/V/IX; mutagenesis; platelet;
D O I
10.1042/BJ20041836
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Binding of the platelet GPIb/V/IX (glycoprotein Ib/V/IX) receptor to von Willebrand factor is critical for platelet adhesion and aggregation under conditions of rapid blood flow. The adhesive function of GPIbα is regulated by its anchorage to the membrane skeleton through a specific interaction with filamin A. In the present study, we examined the amino acid residues within the cytoplasmic tail of GPIba, which are critical for association with filamin A, using a series of 25-mer synthetic peptides that mimic the cytoplasmic tail sequences of wild-type and mutant forms of GPIba. Peptide binding studies of purified human filamin A have demonstrated a major role for the conserved hydrophobic stretch (LFLWV571)-F-567 in mediating this interaction. Progressive alanine substitutions of triple, double and single amino acid residues within the Pro(561)-Arg(572) region suggested an important role for Trp(570) and Phe(568) in promoting GPIbα binding to filamin A. The importance of these two residues in promoting filamin A binding to GPIbα in vivo was confirmed from the study of Chinese-hamster ovary cells expressing GPIbα Trp(570) → Ala and Phe(568) → Ala substitutions. Phenotypic analysis of these cell lines in flow-based adhesion studies revealed a critical role for these residues in maintaining receptor anchorage to the membrane skeleton and in maintaining cell adhesion to a von Willebrand factor matrix under high-shear conditions. These studies demonstrate a novel filamin A binding motif in the cytoplasmic tail of GPIbα, which is critically dependent on both Trp(570) and Phe(568).
引用
收藏
页码:849 / 858
页数:10
相关论文
共 30 条
[1]  
Berndt MC, 2001, THROMB HAEMOSTASIS, V86, P178
[2]   Glycoprotein (GP) Ib-IX-transfected cells roll on a von Willebrand factor matrix under flow - Importance of the GPIb/actin-binding protein (ABP-280) interaction in maintaining adhesion under high shear [J].
Cranmer, SL ;
Ulsemer, P ;
Cooke, BM ;
Salem, HH ;
de la Salle, C ;
Lanza, F ;
Jackson, SP .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (10) :6097-6106
[3]   The cytoplasmic domain of the alpha-subunit of glycoprotein (GP) Ib mediates attachment of the entire GP Ib-IX complex to the cytoskeleton and regulates von Willebrand factor-induced changes in cell morphology [J].
Cunningham, JG ;
Meyer, SC ;
Fox, JEB .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1996, 271 (19) :11581-11587
[4]   The cytoplasmic domain of glycoprotein (GP) Ib alpha constrains the lateral diffusion of the GP Ib-IX complex and modulates von Willebrand factor binding [J].
Dong, JF ;
Li, CQ ;
SaeTung, G ;
Hyun, W ;
AfsharKharghan, V ;
Lopez, JA .
BIOCHEMISTRY, 1997, 36 (41) :12421-12427
[5]   Identification of a finding sequence for the 14-3-3 protein within the cytoplasmic domain of the adhesion receptor, platelet glycoprotein Ib alpha [J].
Du, XP ;
Fox, JE ;
Pei, S .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1996, 271 (13) :7362-7367
[6]   Regulation of von Willebrand factor finding to the platelet glycoprotein Ib-IX by a membrane skeleton-dependent inside-out signal [J].
Englund, GD ;
Bodnar, RJ ;
Li, ZY ;
Ruggeri, ZM ;
Du, XP .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (20) :16952-16959
[7]   Different binding motifs in metabotropic glutamate receptor type 7b for filamin A, protein phosphatase 1C, protein interacting with protein kinase C (PICK) 1 and syntenin allow the formation of multimeric protein complexes [J].
Enz, R ;
Croci, C .
BIOCHEMICAL JOURNAL, 2003, 372 (372) :183-191
[8]   The actin-binding protein Filamin-A interacts with the metabotropic glutamate receptor type 7 [J].
Enz, R .
FEBS LETTERS, 2002, 514 (2-3) :184-188
[9]   Filamin A binding to the cytoplasmic tail of glycoprotein Ibα regulates von Willebrand factor-induced platelet activation [J].
Feng, SJ ;
Reséndiz, JC ;
Lu, X ;
Kroll, MH .
BLOOD, 2003, 102 (06) :2122-2129