RRC ID 33053
著者 Lyulcheva E, Taylor E, Michael M, Vehlow A, Tan S, Fletcher A, Krause M, Bennett D.
タイトル Drosophila pico and its mammalian ortholog lamellipodin activate serum response factor and promote cell proliferation.
ジャーナル Dev Cell
Abstract MIG-10/RIAM/lamellipodin (MRL) proteins link activated Ras-GTPases with actin regulatory Ena/VASP proteins to induce local changes in cytoskeletal dynamics and cell motility. MRL proteins alter monomeric (G):filamentous (F) actin ratios, but the impact of these changes had not been fully appreciated. We report here that the Drosophila MRL ortholog, pico, is required for tissue and organismal growth. Reduction in pico levels resulted in reduced cell division rates, growth retardation, increased G:F actin ratios and lethality. Conversely, pico overexpression reduced G:F actin ratios and promoted tissue overgrowth in an epidermal growth factor (EGF) receptor (EGFR)-dependent manner. Consistently, in HeLa cells, lamellipodin was required for EGF-induced proliferation. We show that pico and lamellipodin share the ability to activate serum response factor (SRF), a transcription factor that responds to reduced G:F-actin ratios via its co-factor Mal. Genetics data indicate that mal/SRF levels are important for pico-mediated tissue growth. We propose that MRL proteins link EGFR activation to mitogenic SRF signaling via changes in actin dynamics.
巻・号 15(5)
ページ 680-90
公開日 2008-11-1
DOI 10.1016/j.devcel.2008.09.020
PII S1534-5807(08)00402-4
PMID 19000833
PMC PMC2691947
MeSH Animals Carrier Proteins / metabolism* Cell Proliferation* DNA-Binding Proteins / metabolism Drosophila / genetics Drosophila / growth & development Drosophila / metabolism* Drosophila Proteins / metabolism* ErbB Receptors / metabolism Humans Membrane Proteins / metabolism* Serum Response Factor / metabolism Signal Transduction
IF 10.092
引用数 33
WOS 分野 DEVELOPMENTAL BIOLOGY CELL BIOLOGY
リソース情報
ショウジョウバエ 11940R-2 11940R-3