Phosphatase Signaling in Physiology and Disease
Group leader: Anita Boratkó, Ph.D. (boratko@med.unideb.hu)
Group members:
Bálint Bécsi (Ph.D) assistant professor
Márton Fonódi, research assistant
Assala Raya, Ph.D student
Fanni Szalmás, Ph.D student
Karolina Kovács, laboratory assistant
TDK students:
Zohair Khan
Kent Duong
Andrade Cedeno Hugo Ernesto
Pramudya Rengganis Ayu
Research background:
Serine/threonine protein phosphatases are essential regulators of intracellular signaling, balancing the activity of protein kinases through the reversible dephosphorylation of target proteins. Among these enzymes, Protein Phosphatase 1 (PP1), Protein Phosphatase 2A (PP2A), and Protein Phosphatase 2B (PP2B, also known as calcineurin) represent major phosphatase families that control a wide range of cellular processes. Their activity influences cell proliferation, cytoskeletal organization, barrier function, calcium-dependent signaling, and stress responses. Because these processes are central to cellular homeostasis, alterations in phosphatase regulation have been implicated in numerous pathological conditions, including vascular disorders, neurodegenerative diseases, and cancer. Importantly, the functional specificity of these phosphatases is largely determined by their regulatory subunits, which guide them to particular substrates and cellular compartments and thereby shape cell type–specific signaling outcomes.
The research group focuses on understanding how serine/threonine phosphatases regulate signaling networks in different cellular contexts and how their dysregulation contributes to disease-related processes. A major emphasis of our work is the study of PP1 and its regulatory subunits that determine its localization and substrate specificity. In particular, we investigate TIMAP (TGF-β Inhibited Membrane Associated Protein), a PP1 regulatory targeting subunit that directs the phosphatase to membrane-associated signaling complexes. Through this interaction, the PP1–TIMAP complex participates in the regulation of cytoskeletal organization, cell–cell junctions, and cellular barrier properties. Understanding how TIMAP controls PP1 activity and targeting is therefore a central question in our research.
To explore phosphatase signaling in physiologically relevant contexts, our studies employ several complementary cellular model systems. We use endothelial cells, neuronal cells, and adenocarcinoma cell lines as experimental models that together represent key physiological and pathological environments in which phosphatase signaling plays a critical role. These systems allow us to investigate how PP1, PP2A, and PP2B regulate signaling pathways controlling cytoskeletal dynamics, barrier integrity, calcium-dependent signaling, and cell survival. By analyzing these phosphatase pathways across multiple cell types, we aim to identify common regulatory principles as well as cell type–specific mechanisms that determine phosphatase function. This integrative approach helps reveal how phosphatase-centered signaling networks contribute to normal cellular physiology and how their dysregulation may drive disease-related alterations in vascular, neuronal, and tumor cell behavior.
Selected publications:
Fonódi M, Nagy L, Boratkó A.: Role of Protein Phosphatases in Tumor Angiogenesis: Assessing PP1, PP2A, PP2B and PTPs Activity. (Int J Mol Sci. 2024 Jun 22;25(13):6868. doi: 10.3390/ijms25136868.)
Thalwieser Z, Fonódi M, Király N, Csortos C, Boratkó A.: PP2A Affects Angiogenesis via Its Interaction with a Novel Phosphorylation Site of TSP1. (Int J Mol Sci. 2024 Feb 3;25(3):1844. doi: 10.3390/ijms25031844.)
Boratkó A, Csortos C.: TIMAP, the versatile protein phosphatase 1 regulator in endothelial cells. (IUBMB Life. 2017 Dec;69(12):918-928. doi: 10.1002/iub.1695. Epub 2017 Nov 15.)
Fonódi M, Thalwieser Z, Csortos C, Boratkó A : TIMAP, a Regulatory Subunit of Protein Phosphatase 1, Inhibits In Vitro Neuronal Differentiation. (Int J Mol Sci. 2023 Dec 11;24(24):17360. doi: 10.3390/ijms242417360.)