Characterisation of an evolutionary conserved protein interacting with the putative guanine nucleotide exchange factor DelGEF and modulating secretion.

A human cDNA library was screened for proteins interacting with the deafness locus putative guanine nucleotide exchange factor (DelGEF) using a yeast two-hybrid system. A protein with a predicted size of 9 kDa was identified as a binding partner, this protein was designated DelGEF interacting protein 1 (DelGIP1). The interaction between DelGEF and DelGIP1 was verified by co-immunoprecipitation of a DelGEF-DelGIP1 complex from cell lysates. Highly conserved homologues of DelGIP1 were identified in higher and lower eukaryotes by database searching. The human DelGIP1 gene is ubiquitously expressed as judged by human multiple tissue Northern blot analysis. DelGEF was recently shown to interact with Sec5, a protein involved in secretion, and to regulate secretion of proteoglycans. Downregulation of endogenous DelGIP1 in HeLa cells induced increased extracellular secretion of proteoglycans indicating a possible role for DelGIP1 in the secretion process.