title: Stathmin interaction with a putative kinase and coiled-coil-forming protein domains.
abstract: Stathmin is a ubiquitous, cytosolic 19-kDa protein, which is phosphorylated on up to four sites in response to many regulatory signals within cells. Its molecular characterization indicates a functional organization including an N-terminal regulatory domain that bears the phosphorylation sites, linked to a putative alpha-helical binding domain predicted to participate in coiled-coil, protein-protein interactions. We therefore proposed that stathmin may play the role of a relay integrating diverse intracellular regulatory pathways; its action on various target proteins would be a function of its combined phosphorylation state. To search for such target proteins, we used the two-hybrid screen in yeast, with stathmin as a "bait." We isolated and characterized four cDNAs encoding protein domains that interact with stathmin in vivo. One of the corresponding proteins was identified as BiP, a member of the hsp70 heat-shock protein family. Another is a previously unidentified, putative serine/threonine kinase, KIS, which might be regulated by stathmin or, more likely, be part of the kinases controlling its phosphorylation state. Finally, two clones code for subdomains of two proteins, CC1 and CC2, predicted to form alpha-helices participating in coiled-coil interacting structures. Their isolation by interaction screening further supports our model for the regulatory function of stathmin through coiled-coil interactions with diverse downstream targets via its presumed alpha-helical binding domain. The molecular and biological characterization of KIS, CC1, and CC2 proteins will give further insights into the molecular functions and mechanisms of action of stathmin as a relay of integrated intracellular regulatory pathways.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, Unité 153, Paris, France.
authors.forename: A
authors.initials: A
authors.lastname: Maucuer
authors.forename: J H
authors.initials: JH
authors.lastname: Camonis
authors.forename: A
authors.initials: A
authors.lastname: Sobel
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000071183:Autophagy-Related Proteins; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D001483:Base Sequence; D004268:DNA-Binding Proteins; D056827:Endosomal Sorting Complexes Required for Transport; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D008868:Microtubule Proteins; D008969:Molecular Sequence Data; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction / Q000235:genetics; D050777:Stathmin; D014018:Tissue Distribution; D014157:Transcription Factors; D000099177:Tsg101 Protein
chemical_list: D000071183:Autophagy-Related Proteins; D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; D056827:Endosomal Sorting Complexes Required for Transport; D018840:HSP70 Heat-Shock Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008868:Microtubule Proteins; D010750:Phosphoproteins; D017346:Protein Serine-Threonine Kinases; D011506:Proteins; D011993:Recombinant Fusion Proteins; D050777:Stathmin; D014157:Transcription Factors; D000099177:Tsg101 Protein; C068354:Kis protein, Bacteria; C428743:Rb1cc1 protein, mouse; C493994:Stmn1 protein, mouse; C530659:Uhmk1 protein, mouse