Interplay of PKA and Rac: Fine-tuning of Rac localization and signaling
Open accessAbstract
Cellular membrane receptors sense environmental changes and relay the reshaped signal through spatially and temporally organized protein-protein interactions (PPI). Many of such PPI are transient and occur in a certain cell-dependent context. Molecular switches such as kinases and GTPases are engaged in versatile PPI. Recently, we have identified dynamic interaction and reciprocal regulation of cAMP-dependent protein kinase A (PKA) and Rho-GTPase Rac signaling. We demonstrated that GTP-activated Rac acts as a dual kinase-tuning scaffold for p21-activated kinase (PAK) and PKA activities. We showed that receptor-triggered PKA trans-phosphorylation of GTP-Rac-organized PAK contributes to elevations of nuclear Erk1/2 signaling and proliferation. We discuss these recent observations and we provide additional insights how the cAMP-PKA axis might also participate in the regulation of Rac localization.
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PKA can form a complex with Rac1 that induces constitutive Rac1 activity.
“Interestingly, PKA can form a complex with Rac1 that induces constitutive Rac1 activity133, a mechanism that may contribute to stress-induced spine loss.”
From Stress weakens prefrontal networks: molecular insults to higher cognition (2015) · cites this paper as [133]
The Abstract reports that PKA forms complexes with GTP-loaded Rac1. It does not support the claim that this complex induces constitutive Rac1 activity: it says complex formation depends on Rac1’s GTP loading and that PKA activity had no direct impact on Rac1 GTP loading in HEK293 cells. (LLM, conf=0.90)
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Background
- Authors
- Bachmann, V. A., Bister, K., & Stefan, E.
- Affiliations
- Universität Innsbruck (AT)
- Corresponding author
- Stefan, Eduard
- Venue
- Small GTPases
- Publisher
- Informa UK Limited
- Published
- 2013-10
- Volume
- 4
- Issue
- 4
- Pages
- 247-251
- ISSN
- 2154-1248 (ISSN-L)
- 2154-1256
- PMC
- PMC4011821
- OpenAlex
- W2011719452
- Cited by
- 14
- References
- 37
- Citations by year
- 2025: 1 · 2024: 2 · 2022: 2 · 2020: 3 · 2018: 2 · 2016: 1 · 2015: 3
- FWCI
- 0.60
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc
- Locations
- Small GTPases (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Funders
- Austrian Science Fund
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
- Keywords
- protein kinase A, Rac GTPase, p21-activated kinase, protein-protein interaction, transphosphorylation, ERK signaling, cell proliferation, cAMP signaling, GTPase signaling
- MeSH terms
- Cyclic AMP, Female, Humans, Multienzyme Complexes, Cyclic AMP-Dependent Protein Kinases, rac1 GTP-Binding Protein, MAP Kinase Signaling System
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