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PMID:21139050

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Citation

Fan, C, Fu, Z, Su, Q, Angelini, DJ, Van Eyk, J and Johns, RA (2011) S100A11 mediates hypoxia-induced mitogenic factor (HIMF)-induced smooth muscle cell migration, vesicular exocytosis, and nuclear activation. Mol. Cell Proteomics 10:M110.000901

Abstract

Hypoxia-induced mitogenic factor (HIMF) is a newly discovered protein that is up-regulated in murine models of pulmonary arterial hypertension and asthma. Our previous study shows that HIMF is a potent mitogenic, angiogenic, and vasoconstrictive chemokine associated with pulmonary arterial hypertension. Two-dimensional gel electrophoresis was used to investigate downstream molecules in HIMF-induced cell signaling, demonstrating that S100A11, an EF-hand calcium-binding protein, was exclusively altered and was decreased (2.7±0.2-fold, p<0.05) in pulmonary artery smooth muscle cells (SMCs) treated with HIMF for 5 min compared with untreated cells (n=4). Immunofluorescence showed that in control cells S100A11 is a cytosolic protein, which then aggregates and translocates both to the plasma membrane with subsequent exocytosis and to the nucleus upon HIMF stimulation. Annexin A2, a known S100A11 binding partner, also colocalized with S100A11 during HIMF-induced membrane trafficking. To investigate the intracellular function of S100A11, siRNA was used to knock down S100A11 expression in SMCs. The S100A11 knockdown significantly reduced HIMF-induced SMC migration but did not affect the SMC mitogenic action of HIMF. Our data show that S100A11 mediates HIMF-induced smooth muscle cell migration, vesicular exocytosis, and nuclear activation.

Links

PubMed PMC3047144 Online version:10.1074/mcp.M110.000901

Keywords

Annexin A2/metabolism; Calcium/metabolism; Cell Movement/drug effects; Cell Nucleus/drug effects; Cell Nucleus/metabolism; Cell Proliferation/drug effects; Down-Regulation/drug effects; Exocytosis/drug effects; Extracellular Space/drug effects; Extracellular Space/metabolism; Humans; Intercellular Signaling Peptides and Proteins/metabolism; Intercellular Signaling Peptides and Proteins/pharmacology; Myocytes, Smooth Muscle/cytology; Protein Transport/drug effects; Pulmonary Artery/cytology; S100 Proteins/metabolism; Secretory Vesicles/drug effects; Secretory Vesicles/metabolism; Signal Transduction/drug effects

Significance

Annotations

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

HUMAN:S10AB

GO:0014911: positive regulation of smooth muscle cell migration

ECO:0000315:

P

Organism: Homo sapiens. Protein Name: Protein S100-A11. Notes: Figure 4C is used. The paper states that “after the knockdown of t S100A11 expression, the cell migration induced by HIMF was significantly blocked (C).” Indeed, the corresponding chart does show that the relative area of the cells has significantly decreased upon mutation of S100A11.

complete
CACAO 12357

HUMAN:S10AB

Colocalizes with

GO:0005886: plasma membrane

ECO:0000314:

C

Organism: Homo sapiens. Protein Name: Protein S100-A11. Notes: Figure 2 is used. As the notes say, “S100A11 is a cytosol protein, spotted and diffusely distributed in the resting cells (A). With continuing HIMF stimulation, S100A11 aggregated and translocated to the plasma membrane and the nucleus (B, C, and D).” Thus, S100A11 localizes with the plasma membrane.

complete
CACAO 12358

HUMAN:S10AB

Colocalizes with

GO:0005634: nucleus

ECO:0000314:

C

Organism: Homo sapiens. Protein Name: Protein S100-A11. Notes: Figure 2 is used. As the notes say, “S100A11 is a cytosol protein, spotted and diffusely distributed in the resting cells (A). With continuing HIMF stimulation, S100A11 aggregated and translocated to the plasma membrane and the nucleus (B, C, and D).” Thus, S100A11 colocalizes with the nucleus.

complete
CACAO 12359

HUMAN:S10AB

NOT

GO:0048660: regulation of smooth muscle cell proliferation

ECO:0000315:

P

Organism: Homo sapiens. Protein Name: Protein S100-A11. Notes: Figure 4D is used. According to the paper, “cell proliferation was evaluated by a direct cell counting assay using a hemocytometer... As shown in D, S100A11 knockdown did not affect the cell proliferation by HIMF.” The corresponding chart does indeed show that cell proliferation does not change much in comparison to other groups when treated with S100A11.

complete
CACAO 12360

Notes

See also

References

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