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Protein Kinases and Phosphatases in Cellular Signaling

Karen L. Leach

10.1002/cphy.cp070110

Source: Supplement 20: Handbook of Physiology, The Endocrine System, Cellular Endocrinology

Originally published: 1998

Published online: January 2011

Full Article on Wiley Online Library



Abstract

The sections in this article are:

1 Protein Kinase and Phosphatase Classification
2 Protein Kinase Structure
2.1 Serine/Threonine Kinases
2.2 Tyrosine Kinases
2.3 Dual‐Specificity Kinases
3 Protein Phosphatase Structure
3.1 Serine/Threonine Phosphatases
3.2 Tyrosine Phosphatases
3.3 Dual‐Specificity Phosphatases
4 Kinase and Phosphatase Regulation
4.1 Localization
4.2 Phosphorylation
4.3 Regulation via Autoinhibitory Domains
4.4 Substrate Specificity
5 Protein Kinase C
5.1 Structure
5.2 Isozyme Specificity
5.3 Isozymes in Cellular Function
6 Calcineurin
6.1 Enzyme Structure
6.2 Isoforms
6.3 Substrate Specificity
6.4 Endogenous Substrates
6.5 T‐Cell Activation
6.6 Nuclear Factor of Activated T Cells as a Substrate
6.7 FK506 and Cyclosporin A as Probes of Calcineurin Action
7 Role of CDC25 in Cell‐Cycle Progression
7.1 Overview of Cell‐Cycle Proteins
7.2 Cdc2
7.3 Cdc25
8 Conclusions
Figure 1. Figure 1.

Structure of protein kinase C (PKC) enzymes. Conserved (C1–4) regions are indicated. C1 contains two cysteine‐rich regions and binds phorbol ester/diacyglycerol (DAG). Atypical PKCs contain only one cysteine‐rich region and do not bind DAG/phorbol ester. C2 is responsible for calcium‐binding activity, and the ATP‐binding site is in C3.
Figure 2. Figure 2.

Schematic of calcineurin A‐subunit, showing the catalytic domain, (CaN B)—binding domain, calmodulin (CaM)‐binding domain, and autoinhibitory domain (AID)
Figure 3. Figure 3.

Schematic of T‐cell calcineurin (CaN) activation pathway. Antigen stimulation of the T‐cell receptor (TCR) results in increased cytosolic calcium levels, resulting in CaN activation. CaN dephosphorylates (either directly or indirectly) the nuclear factor of activated T cells (NFAT). Dephosphorylated NFAT translocates to the nucleus, where it regulates induction of several cytokine genes, including interleukin 2 and tumor necrosis factor‐α.
Figure 4. Figure 4.

Schematic of cdc2 kinase regulation. Cyclin B binds to cdc2, which is phosphorylated on Thr14, Tyr15 (by wee1), and Thr161 (by cdk‐activating kinase [CAK]). The cdc25 phosphatase induces mitosis by dephosphorylating Thr14 and Tyr15. Exit from mitosis is regulated by cyclin degradation and Thr161 dephosphorylation.


Figure 1.

Structure of protein kinase C (PKC) enzymes. Conserved (C1–4) regions are indicated. C1 contains two cysteine‐rich regions and binds phorbol ester/diacyglycerol (DAG). Atypical PKCs contain only one cysteine‐rich region and do not bind DAG/phorbol ester. C2 is responsible for calcium‐binding activity, and the ATP‐binding site is in C3.



Figure 2.

Schematic of calcineurin A‐subunit, showing the catalytic domain, (CaN B)—binding domain, calmodulin (CaM)‐binding domain, and autoinhibitory domain (AID)



Figure 3.

Schematic of T‐cell calcineurin (CaN) activation pathway. Antigen stimulation of the T‐cell receptor (TCR) results in increased cytosolic calcium levels, resulting in CaN activation. CaN dephosphorylates (either directly or indirectly) the nuclear factor of activated T cells (NFAT). Dephosphorylated NFAT translocates to the nucleus, where it regulates induction of several cytokine genes, including interleukin 2 and tumor necrosis factor‐α.



Figure 4.

Schematic of cdc2 kinase regulation. Cyclin B binds to cdc2, which is phosphorylated on Thr14, Tyr15 (by wee1), and Thr161 (by cdk‐activating kinase [CAK]). The cdc25 phosphatase induces mitosis by dephosphorylating Thr14 and Tyr15. Exit from mitosis is regulated by cyclin degradation and Thr161 dephosphorylation.

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Article Title: Protein Kinases and Phosphatases in Cellular Signaling
 

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Karen L. Leach. Protein Kinases and Phosphatases in Cellular Signaling. Compr Physiol 2011, Supplement 20: Handbook of Physiology, The Endocrine System, Cellular Endocrinology: 225-253. First published in print 1998. doi: 10.1002/cphy.cp070110