Evidence that HAX-1 is an interleukin-1 alpha N-terminal binding protein.
During studies aimed at understanding the function of the N-terminal peptide of interleukin-1 alpha (IL-1 NTP, amino acids 1-112), which is liberated from the remainder of IL-1 alpha during intracellular processing, we identified by yeast two-hybrid analysis a putative interacting protein previously designated as HAX-1. In vitro binding studies and transient transfection experiments confirmed that HAX-1 can associate with the IL-1 NTP. HAX-1 was first identified as a protein that associates with HS1, a target of non-receptor protein tyrosine kinases within haematopoietic cells. Recent data have also revealed interactions between HAX-1 and three disparate proteins, polycystin-2 (derived from the PKD2 gene), a protein linked to polycystic kidney disease, cortactin, and Epstein-Barr virus nuclear antigen leader protein (EBNA-LP). Sequence analysis of different HAX-1 binding domains revealed a putative consensus binding motif that is present in various intracellular proteins. Overlapping peptides comprising the IL-1 NTP were synthesized, and binding experiments revealed that discrete peptides were capable of interacting with HAX-1. HAX-1 may serve to retain the IL-1 NTP in the cytoplasm, and complex formation between the IL-1 NTP and HAX-1 may play a role in motility and/or adhesion of cells.
Yin
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Orthopaedic Research Laboratories, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
Morioka
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Towle
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Vidal
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Watanabe
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Weissbach
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D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D015153:Blotting, Western; D002358:Cartilage, Articular / Q000378:metabolism; D002448:Cell Adhesion; D019902:Chondrocytes / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D015723:Gene Library; D006801:Humans; D015151:Immunoblotting; D007375:Interleukin-1 / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry; D010957:Plasmids / Q000378:metabolism; D011233:Precipitin Tests; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000378:metabolism* / Q000502:physiology*; D011994:Recombinant Proteins / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D050396:TRPP Cation Channels; D014018:Tissue Distribution; D014162:Transfection; D020798:Two-Hybrid System Techniques
D048868:Adaptor Proteins, Signal Transducing; D018076:DNA, Complementary; D007375:Interleukin-1; D008565:Membrane Proteins; D010455:Peptides; D011506:Proteins; D011994:Recombinant Proteins; D050396:TRPP Cation Channels; C104759:HAX1 protein, human