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PMID:19000833

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Citation

Lyulcheva, E, Taylor, E, Michael, M, Vehlow, A, Tan, S, Fletcher, A, Krause, M and Bennett, D (2008) Drosophila pico and its mammalian ortholog lamellipodin activate serum response factor and promote cell proliferation. Dev. Cell 15:680-90

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.

Links

PubMed PMC2691947 Online version:10.1016/j.devcel.2008.09.020

Keywords

Animals; Carrier Proteins/metabolism; Cell Proliferation; DNA-Binding Proteins/metabolism; Drosophila/genetics; Drosophila/growth & development; Drosophila/metabolism; Drosophila Proteins/metabolism; Humans; Membrane Proteins/metabolism; Receptor, Epidermal Growth Factor/metabolism; Serum Response Factor/metabolism; Signal Transduction

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

DROME:B7Z043

involved_in

GO:0051302: regulation of cell division

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:M9MSQ5

involved_in

GO:0008361: regulation of cell size

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:M9MSQ5

involved_in

GO:0007444: imaginal disc development

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:M9MSQ5

involved_in

GO:0007015: actin filament organization

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:M9MSQ5

involved_in

GO:0051781: positive regulation of cell division

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:M9MSQ5

involved_in

GO:0048639: positive regulation of developmental growth

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:Q6B4I4

involved_in

GO:0051302: regulation of cell division

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:Q8IQW0

involved_in

GO:0008361: regulation of cell size

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:Q8IQW0

involved_in

GO:0007444: imaginal disc development

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:Q8IQW0

involved_in

GO:0007015: actin filament organization

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:Q8IQW0

involved_in

GO:0051781: positive regulation of cell division

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:Q8IQW0

involved_in

GO:0048639: positive regulation of developmental growth

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:Q8MZ79

involved_in

GO:0051302: regulation of cell division

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:Q8SZH0

involved_in

GO:0008361: regulation of cell size

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:Q8SZH0

involved_in

GO:0007444: imaginal disc development

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:Q8SZH0

involved_in

GO:0007015: actin filament organization

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:Q8SZH0

involved_in

GO:0051781: positive regulation of cell division

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:Q8SZH0

involved_in

GO:0048639: positive regulation of developmental growth

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:ENA

involved_in

GO:0007015: actin filament organization

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:Q9VWB7

involved_in

GO:0008361: regulation of cell size

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:Q9VWB7

involved_in

GO:0007444: imaginal disc development

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:Q9VWB7

involved_in

GO:0007015: actin filament organization

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:Q9VWB7

involved_in

GO:0051781: positive regulation of cell division

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:Q9VWB7

involved_in

GO:0048639: positive regulation of developmental growth

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:Q9VZY2

involved_in

GO:0051302: regulation of cell division

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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