The regulation of MacMARCKS expression by integrin beta3

Integrin-mediated adhesion regulates multiple signaling pathways. Our group previously showed that ectopic expression of different integrin beta-subunits in the neuroepithelial cell line GE11, has distinct effects on cell morphology, actin cytoskeletal organization, and on focal contact distribution...

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Bibliographic Details
Published in:Experimental cell research 2007-04, Vol.313 (6), p.1260-1269
Main Authors: van den Bout, Iman, Truong, Hoa H, Huveneers, Stephan, Kuikman, Ingrid, Danen, Erik H J, Sonnenberg, Arnoud
Format: Article
Language:English
Subjects:
Animals
Cell Line
Cell Movement
Cytoplasm - metabolism
Down-Regulation
Gene Expression Regulation
Humans
Integrin alpha5 - metabolism
Integrin alphaVbeta3 - metabolism
Integrin beta3 - genetics
Integrin beta3 - metabolism
Integrin beta3 - physiology
Intracellular Signaling Peptides and Proteins - metabolism
MAP Kinase Signaling System
Membrane Proteins - metabolism
Membrane Proteins - physiology
Mice
Myristoylated Alanine-Rich C Kinase Substrate
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Summary:Integrin-mediated adhesion regulates multiple signaling pathways. Our group previously showed that ectopic expression of different integrin beta-subunits in the neuroepithelial cell line GE11, has distinct effects on cell morphology, actin cytoskeletal organization, and on focal contact distribution. In this report we have investigated changes in gene transcription levels resulting from overexpression of the integrin beta3 subunit. We found that beta3 overexpression leads to the transcriptional downregulation of MARCKS related protein (MRP) resulting in a decreased expression of the MRP protein. Furthermore, we show that the Ras/MAPK pathway controls the basal level of MRP expression but beta3 overexpression bypasses this pathway downstream of ERK to downregulate MRP. Further studies indicate that a region of the cytoplasmic tail of beta3 containing part of the NITY motif is responsible for increased cell spreading and MRP downregulation. However, MRP overexpression failed to inhibit the beta3-induced increase in cell spreading while the knock down of MRP expression in GE11 cells did not increase cell spreading. We suggest that the downregulation of MRP by beta3 is not required for increased cell spreading but instead that MRP downregulation is a secondary effect of increased cell spreading.
ISSN:0014-4827