Regulation of anchorage-dependent signal transduction by protein kinase A and p21-activated kinase - PubMed (original) (raw)
Regulation of anchorage-dependent signal transduction by protein kinase A and p21-activated kinase
A K Howe et al. Nat Cell Biol. 2000 Sep.
Abstract
Activation of the canonical mitogen-activated protein kinase (MAPK) cascade by soluble mitogens is blocked in non-adherent cells. It is also blocked in cells in which the cAMP-dependent protein kinase (PKA) is activated. Here we show that inhibition of PKA allows anchorage-independent stimulation of the MAPK cascade by growth factors. This effect is transient, and its duration correlates with sustained tyrosine phosphorylation of paxillin and focal-adhesion kinase (FAK) in non-adherent cells. The effect is sensitive to cytochalasin D, implicating the actin cytoskeleton as an important factor in mediating this anchorage-independent signalling. Interestingly, constitutively active p21-activated kinase (PAK) also allows anchorage-independent MAPK signalling. Furthermore, PKA negatively regulates PAK in vivo, and whereas the induction of anchorage-independent signaling resulting from PKA suppression is blocked by dominant negative PAK, it is markedly prolonged by constitutively active PAK. These observations indicate that PKA and PAK are important regulators of anchorage-dependent signal transduction.
Comment in
- cAMP takes control.
Frisch SM. Frisch SM. Nat Cell Biol. 2000 Sep;2(9):E167-8. doi: 10.1038/35023650. Nat Cell Biol. 2000. PMID: 10980716 Review. No abstract available.
Similar articles
- Soluble collagen VI induces tyrosine phosphorylation of paxillin and focal adhesion kinase and activates the MAP kinase erk2 in fibroblasts.
Rühl M, Johannsen M, Atkinson J, Manski D, Sahin E, Somasundaram R, Riecken EO, Schuppan D. Rühl M, et al. Exp Cell Res. 1999 Aug 1;250(2):548-57. doi: 10.1006/excr.1999.4540. Exp Cell Res. 1999. PMID: 10413607 - A role for JNK-paxillin signaling in cell migration.
Huang C, Jacobson K, Schaller MD. Huang C, et al. Cell Cycle. 2004 Jan;3(1):4-6. Cell Cycle. 2004. PMID: 14657652 Review. - [Signal crosstalk between cell-substratum adhesion and cell-cell adhesion].
Yano H. Yano H. Tanpakushitsu Kakusan Koso. 2006 May;51(6 Suppl):660-5. Tanpakushitsu Kakusan Koso. 2006. PMID: 16719327 Review. Japanese. No abstract available.
Cited by
- Effects of integrin-mediated cell adhesion on plasma membrane lipid raft components and signaling.
Norambuena A, Schwartz MA. Norambuena A, et al. Mol Biol Cell. 2011 Sep;22(18):3456-64. doi: 10.1091/mbc.E11-04-0361. Epub 2011 Jul 27. Mol Biol Cell. 2011. PMID: 21795400 Free PMC article. - Validation of the p21-activated kinases as targets for inhibition in neurofibromatosis type 2.
Yi C, Wilker EW, Yaffe MB, Stemmer-Rachamimov A, Kissil JL. Yi C, et al. Cancer Res. 2008 Oct 1;68(19):7932-7. doi: 10.1158/0008-5472.CAN-08-0866. Cancer Res. 2008. PMID: 18829550 Free PMC article. - Structure, biochemistry, and biology of PAK kinases.
Kumar R, Sanawar R, Li X, Li F. Kumar R, et al. Gene. 2017 Mar 20;605:20-31. doi: 10.1016/j.gene.2016.12.014. Epub 2016 Dec 19. Gene. 2017. PMID: 28007610 Free PMC article. Review. - Regulation of extracellular signal-regulated kinase by cannabinoids in hippocampus.
Derkinderen P, Valjent E, Toutant M, Corvol JC, Enslen H, Ledent C, Trzaskos J, Caboche J, Girault JA. Derkinderen P, et al. J Neurosci. 2003 Mar 15;23(6):2371-82. doi: 10.1523/JNEUROSCI.23-06-02371.2003. J Neurosci. 2003. PMID: 12657697 Free PMC article. - SHOC2 complex-driven RAF dimerization selectively contributes to ERK pathway dynamics.
Boned Del Río I, Young LC, Sari S, Jones GG, Ringham-Terry B, Hartig N, Rejnowicz E, Lei W, Bhamra A, Surinova S, Rodriguez-Viciana P. Boned Del Río I, et al. Proc Natl Acad Sci U S A. 2019 Jul 2;116(27):13330-13339. doi: 10.1073/pnas.1902658116. Epub 2019 Jun 18. Proc Natl Acad Sci U S A. 2019. PMID: 31213532 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Miscellaneous