Signal-regulated activation of serum response factor is mediated by changes in actin dynamics

Cell. 1999 Jul 23;98(2):159-69. doi: 10.1016/s0092-8674(00)81011-9.


Serum response factor (SRF) regulates transcription of many serum-inducible and muscle-specific genes. Using a functional screen, we identified LIM kinase-1 as a potent activator of SRF. We show that SRF activation by LIM kinase-1 is dependent on its ability to regulate actin treadmilling. LIM kinase activity is not essential for SRF activation by serum, but signals depend on alterations in actin dynamics. Studies with actin-binding drugs, the actin-specific C2 toxin, and actin overexpression demonstrate that G-actin level controls SRF. Regulation of actin dynamics is necessary for serum induction of a subset of SRF target genes, including vinculin, cytoskeletal actin, and srf itself, and also suffices for their activation. Actin treadmilling provides a convergence point for both serum- and LIM kinase-1-induced signaling to SRF.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells
  • Actins / metabolism*
  • Animals
  • COS Cells
  • Calcium-Calmodulin-Dependent Protein Kinases / metabolism
  • Cytoskeleton / metabolism
  • DNA-Binding Proteins / metabolism*
  • Flow Cytometry
  • GTP-Binding Proteins / metabolism
  • Gene Expression Regulation / physiology
  • JNK Mitogen-Activated Protein Kinases*
  • Lim Kinases
  • MAP Kinase Kinase 4
  • Mice
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase Kinases*
  • Molecular Sequence Data
  • Nuclear Proteins / metabolism*
  • Phosphorylation
  • Polymers
  • Protein Kinases / metabolism
  • Serum Response Factor
  • Signal Transduction / physiology*
  • Transcription, Genetic / physiology
  • Zinc Fingers / physiology
  • rhoA GTP-Binding Protein


  • Actins
  • DNA-Binding Proteins
  • Nuclear Proteins
  • Polymers
  • Serum Response Factor
  • Protein Kinases
  • Lim Kinases
  • Limk1 protein, mouse
  • Calcium-Calmodulin-Dependent Protein Kinases
  • JNK Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinase 1
  • MAP Kinase Kinase 4
  • Mitogen-Activated Protein Kinase Kinases
  • GTP-Binding Proteins
  • rhoA GTP-Binding Protein

Associated data

  • GENBANK/L18880
  • GENBANK/M32599