Shirish Shenolikar

Protein phosphorylation controls a wide range of physiological processes in mammalian tissues. Phosphorylation state of cellular proteins is controlled by the opposing actions of protein kinases and phosphatases that are regulated by hormones, neurotransmitters, growth factors and other environmental cues. Our research attempts to understand the communication between protein kinases and phosphatases that dictates cellular protein phosphorylation and the cell's response to hormones. Over the last decade, our work has provided critical information about the role of protein phosphatase-1 (PP1) in controlling synaptic function, cell stress, gene expression and growth. We have generated a large repertoire of reagents to decipher PP1's role in signaling pathways in mammalian cells and tissues. Emerging evidence suggests that in many cells, PP1 activity is fine tuned by the protein, inhibitor-1 (I-1). A major focus of our research is to elucidate the role of I-1 in kinase-phosphatase cross-talk and impact of the altered I-1 gene expression seen in several human diseases. Our studies showed that recognition of cellular substrates by PP1 is also directed by its association with a variety of targeting subunits that are themselves also subject to physiological control. Thus, the overall focus of our research is to define the physiological mechanisms that regulate PP1 functions relevant to human health and disease.

Current Appointments & Affiliations

Professor Emeritus of Psychiatry and Behavioral Sciences · 2016 - Present Psychiatry & Behavioral Sciences, Behavioral Medicine & Neurosciences, Psychiatry & Behavioral Sciences

Recent Publications

Integrated stress response plasticity governs normal cell adaptation to chronic stress via the PP2A-TFE3-ATF4 pathway.

Journal Article Cell Death Differ · December 2024 The integrated stress response (ISR) regulates cell fate during conditions of stress by leveraging the cell's capacity to endure sustainable and efficient adaptive stress responses. Protein phosphatase 2A (PP2A) activity modulation has been shown to be suc ... Full text Link to item Cite

PromISR-6, a Guanabenz Analogue, Improves Cellular Survival in an Experimental Model of Huntington's Disease.

Journal Article ACS Chem Neurosci · August 21, 2019 Guanabenz (GBZ), an α2-adrenergic agonist, demonstrated off-target effects that restored protein homeostasis and ameliorated pathobiology in experimental models of neurodegenerative disease. However, GBZ did not directly activate the integrated stress resp ... Full text Link to item Cite

Protein Phosphatase 1α and Cofilin Regulate Nuclear Translocation of NF-κB and Promote Expression of the Anti-Inflammatory Cytokine Interleukin-10 by T Cells.

Journal Article Mol Cell Biol · November 15, 2018 While several protein serine/threonine kinases control cytokine production by T cells, the roles of serine/threonine phosphatases are largely unexplored. Here, we analyzed the involvement of protein phosphatase 1α (PP1α) in cytokine synthesis following cos ... Full text Open Access Link to item Cite

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Education, Training & Certifications

University of Leeds (United Kingdom) · 1975 Ph.D.

University College London (United Kingdom) · 1971 B.S.

Shirish Shenolikar

Overview

Current Appointments & Affiliations

Recent Publications

Integrated stress response plasticity governs normal cell adaptation to chronic stress via the PP2A-TFE3-ATF4 pathway.

PromISR-6, a Guanabenz Analogue, Improves Cellular Survival in an Experimental Model of Huntington's Disease.

Protein Phosphatase 1α and Cofilin Regulate Nuclear Translocation of NF-κB and Promote Expression of the Anti-Inflammatory Cytokine Interleukin-10 by T Cells.

Recent Grants

Phosphatase Inhibitor 1, An Amplifier of cAMP Signals

Protein Phosphatase-1 - Targeting the Cytoskeleton

The molecular basis of secretory diarrhea

Education, Training & Certifications