title: Interaction codes within the family of mammalian Phox and Bem1p domain-containing proteins.
abstract: The Phox and Bem1p (PB1) domain constitutes a recently recognized protein-protein interaction domain found in the atypical protein kinase C (aPKC) isoenzymes, lambda/iota- and zeta PKC; members of mitogen-activated protein kinase (MAPK) modules like MEK5, MEKK2, and MEKK3; and in several scaffold proteins involved in cellular signaling. Among the last group, p62 and Par6 (partitioning-defective 6) are involved in coupling the aPKCs to signaling pathways involved in cell survival, growth control, and cell polarity. By mutation analyses and molecular modeling, we have identified critical residues at the interaction surfaces of the PB1 domains of aPKCs and p62. A basic charge cluster interacts with an acidic loop and helix both in p62 oligomerization and in the aPKC-p62 interaction. Subsequently, we determined the abilities of mammalian PB1 domain proteins to form heteromeric and homomeric complexes mediated by this domain. We report several novel interactions within this family. An interaction between the cell polarity scaffold protein Par6 and MEK5 was found. Furthermore, p62 interacts both with MEK5 and NBR1 in addition to the aPKCs. Evidence for involvement of p62 in MEK5-ERK5 signaling is presented.
authors.affiliation: Biochemistry Department, Institute of Medical Biology, University of Tromsø, 9037 Tromsø, Norway.
authors.forename: Trond
authors.initials: T
authors.lastname: Lamark
authors.forename: Maria
authors.initials: M
authors.lastname: Perander
authors.forename: Heidi
authors.initials: H
authors.lastname: Outzen
authors.forename: Kurt
authors.initials: K
authors.lastname: Kristiansen
authors.forename: Aud
authors.initials: A
authors.lastname: Øvervatn
authors.forename: Espen
authors.initials: E
authors.lastname: Michaelsen
authors.forename: Geir
authors.initials: G
authors.lastname: Bjørkøy
authors.forename: Terje
authors.initials: T
authors.lastname: Johansen
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D002352:Carrier Proteins / Q000737:chemistry*; D002460:Cell Line; D004252:DNA Mutational Analysis; D018076:DNA, Complementary / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D049452:Green Fluorescent Proteins; D006367:HeLa Cells; D006801:Humans; D017874:Immediate-Early Proteins / Q000737:chemistry*; D015151:Immunoblotting; D047908:Intracellular Signaling Peptides and Proteins; D008164:Luminescent Proteins / Q000378:metabolism; D048671:MAP Kinase Kinase 5; D008856:Microscopy, Fluorescence; D020929:Mitogen-Activated Protein Kinase Kinases / Q000737:chemistry*; D008957:Models, Genetic; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D010957:Plasmids / Q000378:metabolism; D011233:Precipitin Tests; D011485:Protein Binding; D011493:Protein Kinase C / Q000737:chemistry; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D000071456:Sequestosome-1 Protein; D015398:Signal Transduction; D020798:Two-Hybrid System Techniques
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D018076:DNA, Complementary; D017874:Immediate-Early Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008164:Luminescent Proteins; C549756:NBR1 protein, human; D011506:Proteins; D011993:Recombinant Fusion Proteins; C099718:SQSTM1 protein, human; D000071456:Sequestosome-1 Protein; D049452:Green Fluorescent Proteins; D005982:Glutathione Transferase; D011493:Protein Kinase C; D048671:MAP Kinase Kinase 5; C482563:MAP2K5 protein, human; D020929:Mitogen-Activated Protein Kinase Kinases