An FF domain-dependent protein interaction mediates a signaling pathway for growth factor-induced gene expression.
FF domains are poorly understood protein motifs found in all eukaryotes but in a very small number of proteins. They typically occur in tandem arrays and appear predominantly in splicing and transcription factors. Curiously, they are also present in the p190 family of cytoplasmic Rho GTPase activating proteins (GAPs). We identified the serum-responsive transcriptional regulator TFII-I as a specific interactor with the p190 RhoGAP FF domains. p190 sequesters TFII-I in the cytoplasm via the FF domains, but upon PDGF receptor-mediated phosphorylation of an FF domain, TFII-I is released from p190 and translocates to the nucleus where it can activate transcription of serum-inducible genes including c-fos. These findings reveal a pathway by which mitogens promote gene transcription and indicate a role for FF domains in phosphorylation-mediated signal transduction.
Jiang
Wei
W
Massachusetts General Hospital Cancer Center and Harvard Medical School, Charlestown, MA 02129, USA.
Sordella
Raffaella
R
Chen
Guang-Chao
GC
Hakre
Shweta
S
Roy
Ananda L
AL
Settleman
Jeffrey
J
D021581:Active Transport, Cell Nucleus; D000595:Amino Acid Sequence; D000818:Animals; D002453:Cell Cycle; D002460:Cell Line; D004268:DNA-Binding Proteins; D020690:GTPase-Activating Proteins; D015870:Gene Expression; D016762:Genes, fos; D020662:Guanine Nucleotide Exchange Factors / Q000737:chemistry* / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000737:chemistry* / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D011401:Promoter Regions, Genetic; D017434:Protein Structure, Tertiary; D017479:Receptors, Platelet-Derived Growth Factor / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins; D015398:Signal Transduction; D019473:Transcription Factors, TFII / Q000378:metabolism; D014443:Tyrosine / Q000737:chemistry
C513041:Arhgap35 protein, mouse; C513042:Arhgap5 protein, mouse; D004268:DNA-Binding Proteins; C104259:GTF2I protein, human; D020690:GTPase-Activating Proteins; D020662:Guanine Nucleotide Exchange Factors; D009687:Nuclear Proteins; D010982:Platelet-Derived Growth Factor; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D019473:Transcription Factors, TFII; D014443:Tyrosine; D017479:Receptors, Platelet-Derived Growth Factor