Linked Life Data

8245475

Source:http://linkedlifedata.com/resource/pubmed/id/8245475

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
1994-1-6
pubmed:abstractText
To define the structural features important for IL-8 binding to its two known receptors, mutants of IL-8 and melanoma growth-stimulating activity (MGSA) and chimerae consisting of segments of these two chemokines were constructed and purified from the pGEX 2T Escherichia coli expression vector. IL-8 alpha and beta receptors were expressed stably and individually in 293 kidney epithelial cells and HL60 human leukemia cells. The Kd for IL-8 itself and copy numbers for both receptors in transfected cells were comparable. Competition binding with 125I-labeled IL-8, however, showed large differences for several of the IL-8 mutants between alpha and beta receptors. The amino-terminal ELR sequence was important for IL-8 binding to the alpha receptor, but not sufficient for high affinity binding. Both rabbit IL-8 and MGSA share the ELR sequence with human IL-8, but compete poorly with it. The carboxyl terminus distal to amino acid 50 does not seem to mediate high affinity binding to the alpha receptor. A rabbit IL-8/human IL-8 chimera that differs in only eight amino acids from the human IL-8 sequence, was 150-fold lower in its affinity for the alpha receptor than human IL-8. In contrast, both the amino and carboxyl termini appear to be important for binding to the beta receptor. If the ELR sequence of IL-8 was substituted with alanines or if the carboxyl terminus distal to C50 was replaced with the MGSA sequence, a reduction occurred in binding competition. If both changes were introduced simultaneously, binding was abolished. Binding of MGSA was completely prevented by replacement of the ELR sequence with alanines. Ca2+ mobilization in HL60 cells transfected with the alpha or beta receptor was used to assess cell stimulation. The various mutant forms of IL-8 induced receptor activity with a pattern of sensitivity parallel to the competition binding affinities, indicating that both receptors are active.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
151
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
6418-28
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:8245475-Amino Acid Sequence, pubmed-meshheading:8245475-Base Sequence, pubmed-meshheading:8245475-Binding Sites, pubmed-meshheading:8245475-Calcium, pubmed-meshheading:8245475-Chemokine CXCL1, pubmed-meshheading:8245475-Chemokines, CXC, pubmed-meshheading:8245475-Chemotactic Factors, pubmed-meshheading:8245475-Growth Substances, pubmed-meshheading:8245475-Humans, pubmed-meshheading:8245475-Intercellular Signaling Peptides and Proteins, pubmed-meshheading:8245475-Interleukin-8, pubmed-meshheading:8245475-Molecular Sequence Data, pubmed-meshheading:8245475-Mutation, pubmed-meshheading:8245475-Neoplasm Proteins, pubmed-meshheading:8245475-Receptors, Interleukin, pubmed-meshheading:8245475-Receptors, Interleukin-8A, pubmed-meshheading:8245475-Structure-Activity Relationship
pubmed:year
1993
pubmed:articleTitle
Multiple sites on IL-8 responsible for binding to alpha and beta IL-8 receptors.
pubmed:affiliation
Department of Immunology, Scripps Research Institute, La Jolla, CA 92037.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.