ArticleMolecular and cellular biology1999
p70 S6 kinase is regulated by protein kinase Czeta and participates in a phosphoinositide 3-kinase-regulated signalling complex.
Article in Molecular and cellular biology, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
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Who cites it
62 citing papers in PubMed, 180 citations in OpenAlex.
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- Effect of Physical Exercise on Acute Post-traumatic Hyperexcitability: The Role of Thrombin/PAR1 Signaling.Molecular neurobiology · 2026Article
- Protein Kinase C Family: Structures, Biological Functions, Diseases, and Pharmaceutical Interventions.MedComm · 2025Review
- Melatonin enhances everolimus efficacy in breast cancer by suppressing mTOR pathway activation and promoting apoptosis and mitochondrial function.BMC pharmacology & toxicology · 2025Article
- Restoration of atypical protein kinase C ζ function in autosomal dominant polycystic kidney disease ameliorates disease progression.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Redox regulation of PTPN22 affects the severity of T-cell-dependent autoimmune inflammation.eLife · 2022Article
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- Decreased Whole-Body Fat Mass Produced by Chronic Alcohol Consumption is Associated with Activation of S6K1-Mediated Protein Synthesis and Increased Autophagy in Epididymal White Adipose Tissue.Alcoholism, clinical and experimental research · 2016Article
- PKCζ Is Essential for Pancreatic β-Cell Replication During Insulin Resistance by Regulating mTOR and Cyclin-D2.Diabetes · 2016Article
- Novel PKC-ζ to p47 phox interaction is necessary for transformation from blebbishields.Scientific reports · 2016Article
- AGE-RAGE signal generates a specific NF-κB RelA "barcode" that directs collagen I expression.Scientific reports · 2016Article
- Functional role of RNA polymerase II and P70 S6 kinase in KCl withdrawal-induced cerebellar granule neuron apoptosis.The Journal of biological chemistry · 2015Article
- Sustained PKCβII activity confers oncogenic properties in a phospholipase D- and mTOR-dependent manner.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2014Article
- The translation of translational control by FMRP: therapeutic targets for FXS.Nature neuroscience · 2013Review
- Atypical protein kinase C and Par3 are required for proteoglycan-induced axon growth inhibition.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2013Article
- TPCK inhibits AGC kinases by direct activation loop adduction at phenylalanine-directed cysteine residues.FEBS letters · 2012Article
- Mammalian TOR signaling to the AGC kinases.Critical reviews in biochemistry and molecular biology · 2011Review
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2 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
p70 S6 kinase (p70S6K) is an important regulator of cell proliferation. Its activation by growth factor requires phosphorylation by various inputs on multiple sites. Data accumulated thus far support a model whereby p70S6K activation requires sequential phosphorylations at proline-directed residues in the putative autoinhibitory pseudosubstrate domain, as well as threonine 389. Threonine 229, a site in the catalytic loop is phosphorylated by phosphoinositide-dependent kinase 1 (PDK-1). Experimental evidence suggests that p70S6K activation requires a phosphoinositide 3-kinase (PI3-K)-dependent signal(s). However, the intermediates between PI3-K and p70S6K remain unclear. Here, we have identified PI3-K-regulated atypical protein kinase C (PKC) isoform PKCzeta as an upstream regulator of p70S6K. In coexpression experiments, we found that a kinase-inactive PKCzeta mutant antagonized activation of p70S6K by epidermal growth factor, PDK-1, and activated Cdc42 and PI3-K. While overexpression of a constitutively active PKCzeta mutant (myristoylated PKCzeta [myr-PKCzeta]) only modestly activated p70S6K, this mutant cooperated with PDK-1 activation of p70S6K. PDK-1-induced activation of a C-terminal truncation mutant of p70S6K was also enhanced by myr-PKCzeta. Moreover, we have found that p70S6K can associate with both PDK-1 and PKCzeta in vivo in a growth factor-independent manner, while PDK-1 and PKCzeta can also associate with each other, suggesting the existence of a multimeric PI3-K signalling complex. This work provides evidence for a link between a phorbol ester-insensitive PKC isoform and p70S6K. The existence of a PI3-K-dependent signalling complex may enable efficient activation of p70S6K in cells.
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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.