The formin/diaphanous-related protein, FHOS, interacts with Rac1 and activates transcription from the serum response element.
FHOS is a member of the formin homology (FH) family of proteins and is expressed at high levels in splenic cells. FH proteins link cellular signaling pathways to the actin cytoskeleton and serum response factor-dependent transcription. In these studies, the role of FHOS in Rho family GTPase signaling pathways was analyzed. FHOS interacted with the polybasic domain in the Rac1 C terminus in a guanine nucleotide-independent manner but did not interact with RhoA, Cdc42Hs, Rac2, or Rac3. Intramolecular autoinhibitory interactions between the C terminus of FHOS and an N-terminal region partially overlapping the Rac1 interaction domain were also identified. FHOS truncation mutants lacking the N- or C-terminal autoregulatory domains stimulated transcription of a c-fos serum response element (SRE)-driven reporter. Overexpression of wild-type and mutant (N17 and V12) Rac1 proteins repressed SRE induction by the N-terminal FHOS deletion mutant but not by the C-terminal FHOS deletion mutant. Immunofluorescence studies indicated that the localization of the mutant FHOS proteins might contribute to their differential responses to Rac1. Wild-type FHOS and the N-terminal deletion mutant localized to the perinuclear region and membrane edges. In contrast, the C-terminal FHOS mutants were diffusely localized. These data suggest that FHOS induces transcription from SREs by multiple pathways and that Rac1 may influence the course of some FHOS-induced signaling events.
Westendorf
J J
JJ
Department of Orthopaedic Surgery and University of Minnesota Cancer Center, University of Minnesota, Minneapolis, Minnesota 55455, USA. weste047@tc.umn.edu
D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D019556:COS Cells; D002352:Carrier Proteins / Q000378:metabolism* / Q000502:physiology; D017931:DNA Primers; D005326:Fetal Proteins / Q000378:metabolism* / Q000502:physiology; D000080865:Formins; D051379:Mice; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000378:metabolism* / Q000502:physiology; D011485:Protein Binding; D017386:Sequence Homology, Amino Acid; D027602:Serum Response Element / Q000502:physiology*; D015533:Transcriptional Activation / Q000502:physiology*; D020830:rac1 GTP-Binding Protein / Q000737:chemistry / Q000378:metabolism*
D002352:Carrier Proteins; D017931:DNA Primers; C120021:FHOD1 protein, human; D005326:Fetal Proteins; D000080865:Formins; D009687:Nuclear Proteins; D020830:rac1 GTP-Binding Protein