CXCR1 and CXCR2 activation and regulation. Role of aspartate 199 of the second extracellular loop of CXCR2 in CXCL8-mediated rapid receptor internalization.

CXCR1 and CXCR2 activation and regulation. Role of aspartate 199 of the second extracellular loop of CXCR2 in CXCL8-mediated rapid receptor internalization. Research Abstract Details 

Research Abstract Table of Contents

Jump to the:

CXCR1 and CXCR2 activation and regulation. Role of aspartate 199 of the second extracellular loop of CXCR2 in CXCL8-mediated rapid receptor internalization. Abstract Text:

Mohd W Nasser,Sandeep K Raghuwanshi,Kimberly M Malloy,Pavani Gangavarapu,Joong-Youn Shim,Krishna Rajarathnam,Ricardo M Richardson,

CXCL8 (interleukin-8) interacts with two receptors, CXCR1 and CXCR2, to activate leukocytes. Upon activation, CXCR2 internalizes very rapidly relative to CXCR1 ( approximately 90% versus approximately 10% after 5 min). The C termini of the receptors have been shown to be necessary for internalization but are not sufficient to explain the distinct kinetics of down-regulation. To determine the structural determinant(s) that modulate receptor internalization, various chimeric and point mutant receptors were generated by progressively exchanging specific domains or amino acids between CXCR1 and CXCR2. The receptors were stably expressed in rat basophilic leukemia 2H3 cells and characterized for receptor binding, intracellular Ca(2+) mobilization, phosphoinositide hydrolysis, phosphorylation, internalization, and MAPK activation. The data herein indicate that the second extracellular loop (2ECL) of the receptors is critical for the distinct rate of internalization. Replacing the 2ECL of CXCR2 with that of CXCR1 (B(2ECL)A) or Asp(199) with its CXCR1 valine counterpart (B(D199V)A) delayed CXCR2 internalization similarly to CXCR1. Replacing Asp(199) with Asn (B(D199N)) restored CXCR2 rapid internalization. Structure modeling of the 2ECL of the receptors also suggested that Asp(199) plays a critical role in stabilizing and modulating CXCR2 rapid internalization relative to CXCR1. B(D199N) internalized rapidly but migrated as a single phosphorylated form like CXCR1 ( approximately 75 kDa), whereas B(2ECL)A and B(D199V)A showed slow and fast migrating forms like CXCR2 ( approximately 45 and approximately 65 kDa, respectively) but internalized like CXCR1. These data further undermine the role of receptor oligomerization in CXCL8 receptor internalization. Like CXCR1, B(D199V)A also induced sustained ERK activation and cross-desensitized Ca(2+) mobilization to CCR5 relative to B(D199N) and CXCR2. Altogether, the data suggest that the 2ECL of the CXCL8 receptors is important in modulating their distinct rate of down-regulation and thereby signal length and post-internalization activities.

CXCR1 and CXCR2 activation and regulation. Role of aspartate 199 of the second extracellular loop of CXCR2 in CXCL8-mediated rapid receptor internalization. Publishing Authors By Initials

MW Nasser,SK Raghuwanshi,KM Malloy,P Gangavarapu,JY Shim,K Rajarathnam,RM Richardson,

For similar investigative techniques: genetic techniques: gene transfer techniques: transfection research abstracts see: investigative techniques: genetic techniques: gene transfer techniques: transfection research

PUBMED ID PMID:

MEDLINE DATE:

CXCR1 and CXCR2 activation and regulation. Role of aspartate 199 of the second extracellular loop of CXCR2 in CXCL8-mediated rapid receptor internalization. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: The Journal of biological chemistry

VOLUME: 282

Page Numbers: 6906-15

Journal Abbreviation: J. Biol. Chem.

ISSN: 0021-9258

DAY: 4

MONTH: 01

YEAR: 2007

CXCR1 and CXCR2 activation and regulation. Role of aspartate 199 of the second extracellular loop of CXCR2 in CXCL8-mediated rapid receptor internalization. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 2985121

CXCR1 and CXCR2 activation and regulation. Role of aspartate 199 of the second extracellular loop of CXCR2 in CXCL8-mediated rapid receptor internalization. Keywords Mesh Terms:

KEYWORDS: Transfection

MESH TERMS: metabolism

Chemical & Substance for Abstract: CXCR1 and CXCR2 activation and regulation. Role of aspartate 199 of the second extracellular loop of CXCR2 in CXCL8-mediated rapid receptor internalization. Information

Substance Name: Aspartic Acid

Registry Number: 56-84-8

Grant and Affiliation Information for CXCR1 and CXCR2 activation and regulation. Role of aspartate 199 of the second extracellular loop of CXCR2 in CXCL8-mediated rapid receptor internalization.

AFFILIATION: Julius L. Chambers Biomedical/Biotechnology Research Institute and the Department of Biology, North Carolina Central University, Durham, North Carolina 27707, USA.

Country: United States

AGENCY: United States NIAID

GRANT: AI-38910

ACRONYM: AI

MEDLINETA: J Biol Chem

REFSOURCE:

DATABASENAME:

ACCESSION NUMBER:

Number Hits: 0

CXCR1 and CXCR2 activation and regulation Role of aspartate 199 of the second extracellular loop of CXCR2 in CXCL8-mediated rapid receptor internalization Related Publications

• A randomized controlled trial of the effect of D-cycloserine on extinction and fear conditioning in humans.
• Activating Notch1 mutations are an early event in T-cell malignancy of Ikaros point mutant Plastic/+ mice.
• Acute sympathetic vasoconstriction at rest and during dynamic exercise in cyclists and sedentary humans.
• Average Daily Bout Minutes of Physical Activity Predict Lower BMI Better than Average Daily Minutes: 555: May 30 9:45 AM 10:00 AM.
• Black cohosh: will there ever be an answer or answers?
• CXCR1 and CXCR2 activation and regulation. Role of aspartate 199 of the second extracellular loop of CXCR2 in CXCL8-mediated rapid receptor internalization.
• Chelators at the cancer coalface: desferrioxamine to Triapine and beyond.
• Detection of protein carbonyls in aging liver tissue: A fluorescence-based proteomic approach.
• Dimethyl-acetamide as a cryoprotectant for rainbow trout spermatozoa.
• Effect of aging and caloric restriction on the mitochondrial proteome.
• Effect of vitamin E on vitamin C-induced lymphocytopenia.
• Effects Of Exercise Training And Oral Antioxidant Administration On Arterial Blood Pressure In The Elderly: 1255: Board #18 May 30 11:00 AM - 12:30 PM.
• Epigenetics, disease, and therapeutic interventions.
• Genomewide screens for Escherichia coli genes affecting growth of T7 bacteriophage.
• In vitro methods of assessing the viability of rainbow trout spermatozoa.
• Limitations to vasodilatory capacity and .VO2 max in trained human skeletal muscle.
• Multipotent hematopoietic cells susceptible to alternative double-strand break repair pathways that promote genome rearrangements.
• Nutritional assessment using a microcomputer 2. Programme evaluation.
• Opioid receptors regulate retrieval of infant fear memories: effects of naloxone on infantile amnesia.
• Relationship between Self-Report and Performance Measures of Function: A Systematic Review.
• Reliability and validity of the Eyberg Child Behavior Inventory with African-American and Latino parents of young children.
• Reliability of real-time ultrasound for the assessment of transversus abdominis function.
• Seasonal effects on caprine response to synchronization of estrus and superovulatory treatment.
• Temporal monitoring: Baseline's logical conclusion.
• Thalidomide- and lenalidomide-associated thromboembolism among patients with cancer.
• The health of the human skeletal system for weight bearing against gravity: The role of deloading the musculo-skeletal system in the development of musculoskeletal injury.
• The mouse genome database (MGD): new features facilitating a model system.
• Transcription and mass-spectroscopic proteomic studies of electron transport oxidoreductases in Dehalococcoides ethenogenes.
• Unidirectional prey-predator facilitation: apparent prey enhance predators' foraging success on cryptic prey.
• What causes a crossover step when walking on uneven ground? A study in healthy young women.