Formins in cell signaling.
The founding formin homology protein family members were implicated early on as being involved in regulating cytoskeletal remodeling pathways, as formin protein mutations in Drosophila and yeast lead to obvious actin cytoskeleton defects. The discovery that these proteins associated directly with small Rho family GTPases confirmed these results and greatly enhanced our understanding of their function. The mammalian diaphanous-related formins (DRFs) were subsequently recognized as being involved in activation of serum response factor (SRF), tying formins to transcriptional regulation. In the past few years, much progress has been made in demonstrating how DRFs act as both downstream effectors and upstream modulators of Rho GTPase signaling. These functions are important for regulation of both actin and microtubule cytoskeletal structures, and affect cellular processes such as the establishment of polarity, vesicle movement, and focal adhesion remodeling. The connection of DRFs to the SH3 domain-containing protein, Src, has also been described as being important to several basic cellular functions. While still unresolved, extensive work has been carried out on how DRFs mediate SRF activation, and the importance of this to the regulation of cytoskeletal structure. This review will focus on the role of formins in cytoplasmic signal transduction pathways and the downstream effects on the regulation of gene expression.
Young
Kevin G
KG
Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, ON, Canada K1H 8M5.
Copeland
John W
JW
D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D005326:Fetal Proteins / Q000235:genetics / Q000378:metabolism*; D000080865:Formins; D005786:Gene Expression Regulation; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D020741:rho GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism; D019061:src-Family Kinases / Q000235:genetics / Q000378:metabolism
D005326:Fetal Proteins; D000080865:Formins; D008840:Microfilament Proteins; D009687:Nuclear Proteins; D019061:src-Family Kinases; D020741:rho GTP-Binding Proteins