Role of the amino-terminal domain in regulating interactions of annexin I with membranes: Effects of amino-terminal truncation and mutagenesis of the phosphorylation sites

SummaryActivation of plasma prekallikein and generation of bradykinin are responsible for the angioedema attacks observed with C1inhibitor deficiency. Heterozygous individuals with <50% levels of active C1-inhibitor are susceptible to angioedema attacks indicating a critical need for C1-inhibitor to be present at maximum levels to prevent unwanted prekallikrein activation. Studies with purified proteins do not adequately explain this observation. Therefore to investigate why reduction of C1inhibitor to levels seen in angioedema patients results in excessive kallikrein generation we examined the effect of endothelial cells on the inhibition of kallikrein by C1-inhibitor. Surprisingly, it was found that a C1-inhibitor concentration of greater than 1 µM was needed to inhibit 3 nM kallikrein. We propose that this apparent protection from inhibition was mediated by kallikrein binding to the cells via the heavy chain in a high molecular weight kininogen and zinc independent manner. Protection of kallikrein from inhibition was not observed when C1-inhibitor truncated in the amino-terminal domain by the StcE metalloproteinase was used, which suggests a novel function for this unique domain. The requirement for high concentrations of C1-inhibitor to fully inhibit kallikrein is consistent with the fact that reduced levels of C1-inhibitor result in the kallikrein activation seen in angioedema.

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The role of the amino-terminal domain of tachykinins in neurokinin-1 receptor signaling and desensitization

Neuropeptides ◽

10.1016/s0143-4179(02)00147-6 ◽

2003 ◽

Vol 37 (1) ◽

pp. 30-35 ◽

Cited By ~ 6

Author(s):

Steven R. Vigna

Keyword(s):

Receptor Signaling ◽

Neurokinin 1 Receptor ◽

Amino Terminal ◽

Terminal Domain ◽

Neurokinin 1 ◽

Amino Terminal Domain

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Role of the amino terminal domain in GroES oligomerization

Biochimica et Biophysica Acta (BBA) - Protein Structure and Molecular Enzymology ◽

10.1016/s0167-4838(96)00106-9 ◽

1997 ◽

Vol 1337 (1) ◽

pp. 47-56 ◽

Cited By ~ 4

Author(s):

Oscar Llorca ◽

Klaus Schneider ◽

JoséL. Carrascosa ◽

Enrique Méndez ◽

JoséM. Valpuesta

Keyword(s):

Amino Terminal ◽

Terminal Domain ◽

Amino Terminal Domain

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Mcl-1 in multiple myeloma: role of the unique amino-terminal domain in regulating survival functions, protein half-life, and protein-protein interactions

European Journal Of Haematology ◽

10.1034/j.1600-0609.2003.11415.x ◽

2003 ◽

Vol 70 (4) ◽

pp. 270-270

Author(s):

B. Zhang ◽

I. Gojo ◽

R. Fenton

Keyword(s):

Multiple Myeloma ◽

Protein Interactions ◽

Half Life ◽

Survival Functions ◽

Protein Protein Interactions ◽

Amino Terminal ◽

Terminal Domain ◽

Amino Terminal Domain

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Enhancer Sequences Influence the Role of the Amino-Terminal Domain of Bicoid in Transcription

Molecular and Cellular Biology ◽

10.1128/mcb.23.13.4439-4448.2003 ◽

2003 ◽

Vol 23 (13) ◽

pp. 4439-4448 ◽

Cited By ~ 13

Author(s):

Dechen Fu ◽

Chen Zhao ◽

Jun Ma

Keyword(s):

Dna Binding ◽

Binding Sites ◽

Target Genes ◽

Cooperative Binding ◽

Dependent Manner ◽

Enhancer Element ◽

Amino Terminal ◽

Terminal Domain ◽

Amino Terminal Domain

ABSTRACT Bicoid (Bcd) is a Drosophila melanogaster morphogenetic gradient that controls embryonic patterning by activating target gene expression in a concentration-dependent manner. In this study we describe experiments to determine how different enhancers respond to Bcd distinctively, focusing on two natural Bcd-responsive enhancer elements, hunchback (hb) and knirps (kni). Our results show that, on the hb enhancer element, the amino-terminal domain of Bcd (residues 1 to 91) plays primarily an inhibitory role, whereas on the kni enhancer element this same Bcd domain plays a positive role at low protein concentrations. We further demonstrate that while the amino-terminal domain is largely dispensable for cooperative binding to the hb enhancer element, it is preferentially required for cooperative binding to the kni enhancer element. Alteration of the arrangement of Bcd binding sites in the kni enhancer element reduces the role of the amino-terminal domain in cooperative DNA binding but increases the effectiveness of the self-inhibitory function. In addition, elimination of symmetric pairs of Bcd binding sites in the kni enhancer element reduces both DNA binding and activation by Bcd. We propose that the amino-terminal domain of Bcd is an enhancer-specific switch that contributes to the protein's ability to activate different target genes in distinct manners.

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