title: HSos1 contains a new amino-terminal regulatory motif with specific binding affinity for its pleckstrin homology domain.
abstract: The protein hSos1 is a Ras guanine nucleotide exchange factor. In the present study, we investigated the function of the amino-terminal region of the hSos1 protein, corresponding to the first 600 residues, which includes the Dbl and pleckstrin homology (DH and PH) domains. We demonstrated, using a series of truncated mutants, that this region is absolutely necessary for hSos1 activity. Our results suggest that the first 200 residues (upstream of DH domain), which we called the HF motif on the basis of their homology with histone H2A, may exert negative control over the functional activity of the whole hSos1 protein. In vitro binding analysis showed that the HF motif is able to interact specifically with the PH domain of hSos1. The amino-terminal region of hSos1 may be associated in vivo with an expressed HF motif. These findings document the existence of the HF motif located upstream of the DH domain in the hSos1 protein. This motif may be responsible for the negative control of hSos1, probably by intramolecular binding with the PH domain.
authors.affiliation: Unidad de Biologia Celular, Centro Nacional de Microbiologia, Instituto de Salud Carlos III, 28220 Majadahonda, Madrid, Spain.
authors.forename: Rocío
authors.initials: R
authors.lastname: Jorge
authors.forename: Natasha
authors.initials: N
authors.lastname: Zarich
authors.forename: José Luis
authors.initials: JL
authors.lastname: Oliva
authors.forename: Marta
authors.initials: M
authors.lastname: Azañedo
authors.forename: Natalia
authors.initials: N
authors.lastname: Martínez
authors.forename: Xavier
authors.initials: X
authors.lastname: de la Cruz
authors.forename: José M
authors.initials: JM
authors.lastname: Rojas
mesh_terms: D016475:3T3 Cells; D020816:Amino Acid Motifs; D000818:Animals; D019556:COS Cells; D002460:Cell Line; D017353:Gene Deletion; D017930:Genes, Reporter; D006801:Humans; D020935:MAP Kinase Signaling System; D051379:Mice; D008958:Models, Molecular; D010455:Peptides; D010957:Plasmids / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D020837:SOS1 Protein / Q000737:chemistry* / Q000502:physiology*; D014162:Transfection
chemical_list: D010455:Peptides; D011993:Recombinant Fusion Proteins; D020837:SOS1 Protein