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Gene Review

Fhl2  -  four and a half LIM domains 2

Mus musculus

Synonyms: C76204, FHL-2, Four and a half LIM domains protein 2, SLIM-3, SLIM3, ...
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Disease relevance of Fhl2


High impact information on Fhl2


Biological context of Fhl2

  • To investigate the importance of FHL2 during myoblast differentiation, we performed a yeast two-hybrid screen using a cDNA library derived from myoblasts induced for differentiation [3].
  • Expression of FHL2 counteracts beta-catenin-mediated activation of a TCF/LEF-dependent reporter gene in a dose-dependent and muscle cell-specific manner [3].
  • Moreover, FHL2 coactivates transactivation of the DAX1 promoter by WT1 [5].
  • The importance of this interaction is revealed by the ability of FHL2 to potentiate the synergistic induction of MIS gene expression by WT1/SF1 [5].
  • Using the yeast two-hybrid system, we showed that ADAM-17 interacts with the Four and Half LIM domain 2 protein (FHL2), a LIM domain protein that is involved in multiple protein-protein interaction [6].

Anatomical context of Fhl2


Regulatory relationships of Fhl2


Other interactions of Fhl2

  • Activation of the coactivator four-and-a-half-LIM-only protein FHL2 and the c-fos promoter through inhibition of protein phosphatase 2A [7].
  • The ability to modulate both DAX1 and MIS expression might allow FHL2 to act in the molecular fine tuning of WT1-dependent control mechanisms in the reproductive organs [5].
  • FHL2 is, therefore, an antiosteoclastogenic molecule exerting its effect by attenuating TRAF6-mediated RANK signaling [4].
  • Here we demonstrate coexpression of the LIM-only coactivator FHL2 and WT1 [5].

Analytical, diagnostic and therapeutic context of Fhl2


  1. Fhl2 deficiency results in osteopenia due to decreased activity of osteoblasts. Günther, T., Poli, C., Müller, J.M., Catala-Lehnen, P., Schinke, T., Yin, N., Vomstein, S., Amling, M., Schüle, R. EMBO J. (2005) [Pubmed]
  2. Disruption of four-and-a-half LIM 2 decreases bone mineral content and bone mineral density in femur and tibia bones of female mice. Govoni, K.E., Baylink, D.J., Chen, J., Mohan, S. Calcif. Tissue Int. (2006) [Pubmed]
  3. The LIM-only protein FHL2 interacts with beta-catenin and promotes differentiation of mouse myoblasts. Martin, B., Schneider, R., Janetzky, S., Waibler, Z., Pandur, P., Kühl, M., Behrens, J., von der Mark, K., Starzinski-Powitz, A., Wixler, V. J. Cell Biol. (2002) [Pubmed]
  4. FHL2 inhibits the activated osteoclast in a TRAF6-dependent manner. Bai, S., Kitaura, H., Zhao, H., Chen, J., Müller, J.M., Schüle, R., Darnay, B., Novack, D.V., Ross, F.P., Teitelbaum, S.L. J. Clin. Invest. (2005) [Pubmed]
  5. The LIM-only coactivator FHL2 modulates WT1 transcriptional activity during gonadal differentiation. Du, X., Hublitz, P., Günther, T., Wilhelm, D., Englert, C., Schüle, R. Biochim. Biophys. Acta (2002) [Pubmed]
  6. FHL2 interacts with both ADAM-17 and the cytoskeleton and regulates ADAM-17 localization and activity. Canault, M., Tellier, E., Bonardo, B., Mas, E., Aumailley, M., Juhan-Vague, I., Nalbone, G., Peiretti, F. J. Cell. Physiol. (2006) [Pubmed]
  7. Activation of the coactivator four-and-a-half-LIM-only protein FHL2 and the c-fos promoter through inhibition of protein phosphatase 2A. Johannessen, M., Olsen, P.A., Johansen, B., Seternes, O.M., Moens, U. Biochem. Pharmacol. (2003) [Pubmed]
  8. FHL2 (SLIM3) is not essential for cardiac development and function. Chu, P.H., Bardwell, W.M., Gu, Y., Ross, J., Chen, J. Mol. Cell. Biol. (2000) [Pubmed]
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