ArticleSmall GTPases2011
Signaling of the direction-sensing FAK/RACK1/PDE4D5 complex to the small GTPase Rap1.
Article in Small GTPases, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
10 citing papers in PubMed, 32 citations in OpenAlex.
- PDE10A as a novel diagnostic and therapeutic target in cancer: insights and challenges.Frontiers in oncology · 2025Review
- Phosphodiesterase type 4 anchoring regulates cAMP signaling to Popeye domain-containing proteins.Journal of molecular and cellular cardiology · 2022Article
- Dissecting Pistil Responses to Incompatible and Compatible Pollen in Self-Incompatibility Brassica oleracea Using Comparative Proteomics.The protein journal · 2017Article
- The important role of the receptor for activated C kinase 1 (RACK1) in nasopharyngeal carcinoma progression.Journal of translational medicine · 2016Article
- Kindlin-3 interacts with the ribosome and regulates c-Myc expression required for proliferation of chronic myeloid leukemia cells.Scientific reports · 2015Article
- Protein kinase A-dependent phosphorylation of Rap1 regulates its membrane localization and cell migration.The Journal of biological chemistry · 2013Article
- RACK1 Function in Cell Motility and Protein Synthesis.Genes & cancer · 2013Review
- RACK1 to the future--a historical perspective.Cell communication and signaling : CCS · 2013Article
- RACK1 depletion in a mouse model causes lethality, pigmentation deficits and reduction in protein synthesis efficiency.Cellular and molecular life sciences : CMLS · 2013Article
- RACK1, A multifaceted scaffolding protein: Structure and function.Cell communication and signaling : CCS · 2011Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We recently reported that a complex between focal adhesion kianse (FAK) and the molecular scaffold RACK1 controlled nascent integrin adhesion formation and cell polarization, via peripheral recruitment of the cAMP - degrading PDE4D5 isoform. Here we review and extend these studies by demonstrating that the FAK/RACK1/PDE4D5 'direction-sensing' complex likely functions by signaling, via the guanine nucleotide exchange factor EPAC , to its small GTPase target Rap1. Specifically, activating EPAC suppresses polarization of squamous cancer cells, while, in contrast, modulating PKA, the other major cAMP effector, has no effect. Moreover, FAK-deficient malignant keratinocytes re-expressing a FAK mutant that cannot bind to RACK1, namely FAK-E139A,D140A, display elevated Rap1 that is linked to impaired polarization. Thus, it is likely that the FAK/RACK1/PDE4D5 complex signals to keep Rap1 low at appropriate times and in a spatially-regulated manner as cells first sense their environment and make decisions about nascent adhesion stabilization and polarization. RACK1 is abundantly expressed in both normal and malignant keratinocytes, while FAK and PDE4D5 are both elevated in the cancer cells, suggesting that the FAK/RACK1/PDE4D5/Rap1 signaling axis may contribute to FAK's well documented role in tumor progression.
Identifiers
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.