ArticleBiochemistry2018
Interaction of Calmodulin with the cSH2 Domain of the p85 Regulatory Subunit.
Article in Biochemistry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed.
- Pioneer in Molecular Biology: Conformational Ensembles in Molecular Recognition, Allostery, and Cell Function.Journal of molecular biology · 2025Review
- ACKnowledging the role of the Activated-Cdc42 associated kinase (ACK) in regulating protein stability in cancer.Small GTPases · 2023Review
- Ras isoform-specific expression, chromatin accessibility, and signaling.Biophysical reviews · 2021Review
- Article
- The Role of Calmodulin in Tumor Cell Migration, Invasiveness, and Metastasis.International journal of molecular sciences · 2020Review
- The Structural Basis of the Farnesylated and Methylated KRas4B Interaction with Calmodulin.Structure (London, England : 1993) · 2019Article
- The multifunctional role of phospho-calmodulin in pathophysiological processes.The Biochemical journal · 2018Review
- Calmodulin (CaM) Activates PI3Kα by Targeting the "Soft" CaM-Binding Motifs in Both the nSH2 and cSH2 Domains of p85α.The journal of physical chemistry. B · 2018Article
- Autoinhibition in Ras effectors Raf, PI3Kα, and RASSF5: a comprehensive review underscoring the challenges in pharmacological intervention.Biophysical reviews · 2018Review
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Authors and funding
9 authors.
Funding
Abstract
Calmodulin (CaM) is a calcium sensor protein that directly interacts with the dual-specificity (lipid and protein) kinase PI3Kα through the SH2 domains of the p85 regulatory subunit. In adenocarcinomas, the CaM interaction removes the autoinhibition of the p110 catalytic subunit of PI3Kα, leading to activation of PI3Kα and promoting cell proliferation, survival, and migration. Here we demonstrate that the cSH2 domain of p85α engages its two CaM-binding motifs in the interaction with the N- and C-lobes of CaM as well as the flexible central linker, and our nuclear magnetic resonance experiments provide structural details. We show that in response to binding CaM, cSH2 exposes its tryptophan residue at the N-terminal region to the solvent. Because of the flexible nature of both CaM and cSH2, multiple binding modes of the interactions are possible. Binding of CaM to the cSH2 domain can help release the inhibition imposed on the p110 subunit, similar to the binding of the phosphorylated motif of RTK, or phosphorylated CaM (pCaM), to the SH2 domains. Amino acid sequence analysis shows that CaM-binding motifs are common in SH2 domains of non-RTKs. We speculate that CaM can also activate these kinases through similar mechanisms.
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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.