Src regulates the activity of the mammalian formin protein FHOD1.
The mammalian formin homology domain containing protein FHOD1 influences a variety of cellular events including cell migration, cytoskeletal arrangement, signal transduction, and gene expression. In this paper, we show that Src regulates a variety of FHOD1-associated effects. FHOD1 distribution to lamellipodia was prevented by the absence of Src. However, stress fiber formation induced by a C-terminal truncated form of FHOD1 was unaffected. Gene expression from an SRE-dependent promoter and from the skeletal actin promoter was induced by two truncated forms of FHOD1 and in both instances, inhibition of Src tyrosine kinase activity abrogated induction of gene expression. Furthermore, Src activity was necessary to maintain mRNA levels of FHOD1 itself, and as such, this finding represents the first description of mechanisms involved in the regulation of formin gene expression in mammals. In summary, we have identified Src as a key regulator of FHOD1 biology.
Koka
Sreenivas
S
Department of Dental Specialties, Mayo Clinic, Rochester, Minnesota, USA. koka.sreenivas@mayo.edu
Minick
Gerald T
GT
Zhou
You
Y
Westendorf
Jennifer J
JJ
Boehm
Matthew B
MB
D000199:Actins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D016391:Genes, src; D051379:Mice; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000378:metabolism; D027602:Serum Response Element / Q000235:genetics; D022502:Stress Fibers / Q000378:metabolism; D020741:rho GTP-Binding Proteins / Q000378:metabolism; D019061:src-Family Kinases / Q000235:genetics / Q000502:physiology*
D000199:Actins; D009687:Nuclear Proteins; D012333:RNA, Messenger; D019061:src-Family Kinases; D020741:rho GTP-Binding Proteins