Vinexin β Regulates the Anchorage Dependence of ERK2 Activation Stimulated by Epidermal Growth Factor
ERK is activated by soluble growth factors in adherent cells. However, activation of ERK is barely detectable and not sufficient for cell proliferation in non-adherent cells. Here, we show that exogenous expression of vinexin β, a novel focal adhesion protein, allows anchorage-independent ERK2 acti...
Saved in:
Published in | The Journal of biological chemistry Vol. 277; no. 15; p. 13053 |
---|---|
Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
Published |
American Society for Biochemistry and Molecular Biology
12.04.2002
|
Online Access | Get full text |
Cover
Loading…
Summary: | ERK is activated by soluble growth factors in adherent cells. However, activation of ERK is barely detectable and not sufficient
for cell proliferation in non-adherent cells. Here, we show that exogenous expression of vinexin β, a novel focal adhesion
protein, allows anchorage-independent ERK2 activation stimulated by epidermal growth factor. In contrast, expression of vinexin
β had no effect on ERK2 activation in adherent cells, suggesting that vinexin β regulates the anchorage dependence of ERK2
activation. Analyses using deletion mutants demonstrated that a linker region between the second and third SH3 domains of
vinexin β, but not the SH3 domains, is required for this function of vinexin β. To evaluate the pathway regulating the anchorage
dependence of ERK2 activation, we used a dominant-negative mutant of p21-activated kinase (PAK) and a specific inhibitor (H89)
of cAMP-dependent protein kinase (PKA) because PAK and PKA are known to regulate the anchorage dependence of ERK2 activation.
The dominant-negative mutant of PAK suppressed the anchorage-independent ERK2 activation induced by expression of vinexin
β. The dominant-negative mutant of vinexin β inhibited the anchorage-independent ERK2 activation induced by the PKA inhibitor.
Together, these observations indicate that vinexin β plays a key role in regulating the anchorage dependence of ERK2 activation
through PKA-PAK signaling. |
---|---|
ISSN: | 0021-9258 1083-351X |
DOI: | 10.1074/jbc.M108644200 |