Evidence that HAX-1 is an interleukin-1 alpha N-terminal binding protein

During studies aimed at understanding the function of the N-terminal peptid e 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 identi fied by yeast two-hybrid analysis a putative interacting protein previously designated as HAX-1. In vitro binding studies and transient transfection e xperiments 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-rec eptor protein tyrosine kinases within haematopoietic cells. Recent data hav e also revealed interactions between HAX-1 and three disparate proteins, po lycystin-2 (derived from the PKD2 gene), a protein linked to polycystic kid ney disease, cortactin, and Epstein-Barr virus nuclear antigen leader prote in (EBNA-LP). Sequence analysis of different HAX-1 binding domains revealed a putative consensus binding motif that is present in various intracellula r proteins. Overlapping peptides comprising the IL-1 NTP were synthesized, and binding experiments revealed that discrete peptides were capable of int eracting with HAX-1. HAX-1 may serve to retain the IL-1 NTP in the cytoplas m, and complex formation between the IL-1 NTP and HAX-1 may play a role in motility and/or adhesion of cells. (C) 2001 Academic Press.