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Protein Tyrosine Phosphatase Control of Metabolism pp 71–89Cite as

PTP1B and TCPTP in CNS Signaling and Energy Balance

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Abstract

The regulation of energy balance is under tight homeostatic control. Biological mechanisms have evolved over time to ensure adequate nutritional status and appropriate body composition in response to metabolic and environmental stimuli. The central nervous system (CNS) plays an important role in the regulation of body weight and in the control of normal glucose homeostasis. Several key areas of the CNS are involved in energy balance, including the nuclei of the hypothalamus, hindbrain, and limbic (reward) centers of the brain. Within these brain regions critical cellular signaling pathways have been identified that mediate a multitude of metabolic processes, including feeding, body weight gain/loss, energy expenditure, core temperature regulation, peripheral insulin sensitivity, and liver metabolism. Two such pathways are the leptin and insulin signaling pathways. Rapid reversible phosphorylation events within these key CNS signaling pathways are critical to the tight regulation of energy balance control, and disruption of these events can contribute to the pathogenesis of the metabolic syndrome. Protein tyrosine phosphatases, or PTPs, catalyze the dephosphorylation of phosphorylated tyrosyl residues and thus are important regulators of intracellular signaling pathways. In this chapter, the contributions of protein tyrosine phosphatase 1B (PTP1B) and its closest homologue, T cell PTP (TCPTP), to CNS control of energy balance will be highlighted.

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Abbreviations

AgRP:

Agouti-related peptide

ARC:

Arcuate nucleus

BAT:

Brown adipose tissue

Cga:

Glycoprotein hormone alpha-subunit

CNS:

Central nervous system

DMH:

Dorsomedial hypothalamus

ER:

Endoplasmic reticulum

GH:

Growth hormone

icv :

Intracerebroventricular

IR:

Insulin receptor

IRS-1:

Insulin receptor substrate-1

JAK-2:

Janus-activated kinase 2

LepRb:

Leptin receptor

LH:

Lateral hypothalamus

MEFs:

Mouse embryonic fibroblasts

MTII:

Melanotan II

NPY:

Neuropeptide Y

NTS:

Nucleus of the solitary tract

PI3K:

Phosphatidylinositol 3-kinase

POMC:

Proopiomelanocortin

PTP1B:

Protein tyrosine phosphatase 1B

PVN:

Paraventricular nucleus

SHP-2:

Src homology phosphatase-2

SOCS3:

Suppressor of cytokine signaling 3

TCPTP:

T cell PTP

VMH:

Ventromedial hypothalamus

VTA:

Ventral tegmental area

α-MSH:

α-melanocyte-stimulating hormone

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Acknowledgements

T.T. is a National Health and Medical Research Council (NHMRC) of Australia Principal Research Fellow and supported by grants from the NHMRC. K.B. is an Associate Professor at the University of Pennsylvania, School of Veterinary Medicine, and is supported by the National Institutes of Health (NIDDK).

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  1. Department of Animal Biology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, 19104-6046, USA

    Kendra K. Bence Ph.D.

  2. Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC, 3800, Australia

    Tony Tiganis Ph.D., B.Sc.

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    Kendra K. Bence

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Bence, K.K., Tiganis, T. (2013). PTP1B and TCPTP in CNS Signaling and Energy Balance. In: Bence, K. (eds) Protein Tyrosine Phosphatase Control of Metabolism. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-7855-3_4

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