Regulation of JAKs: Insights Gleaned from the Functional Protein Domains

Haan, Claude; Ungureanu, Daniela; Pekkala, Tuija; Silvennoinen, Olli; Haan, Serge

doi:10.1007/978-3-7091-0891-8_2

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The Signaling Mechanism Likely Is Directionally (Orientation1

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2013

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(2 citation statements)

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“…Other evidence strongly supports that the JAK2 is activated through the steric information transduced through the transmembrane region into the cell. (3,21).…”

Section: The Signaling Mechanism Likely Is Directionally (Orientationmentioning

confidence: 99%

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On the Regulation and Activation of JAK2: A Novel Hypothetical Model

2013

Molecular Cancer Research

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Janus kinase 2 (JAK2) is a protein tyrosine kinase central to a multitude of cellular processes. Here, a novel model of JAK2 regulation and activation is proposed. In the JAK2 dimer, instead of being auto-inhibited by its own JH2 domain, inhibition comes from the JH2 domain of the partnering JAK2 monomer. Upon ligand binding, the receptor undergoes a conformational rotation that is passed to its dimeric partner. The activation is achieved by the rotation of two JAK2 molecules, which relieves the JH1/JH2 inhibitory interface and brings two JH1 domains in proximity for the subsequent trans-phosphorylation event. This hypothetical model is consistent with most of the currently available experimental evidence and warrants further tests. Based on the proposed model, it is possible to rationalize the differential responses of JAK2 signaling involving various receptors and ligands.Implications: The proposed model of JAK2 regulation and activation is poised to suggest potential alternative drug-discovery strategies that could impact a number of relevant diseases.

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“…Other evidence strongly supports that the JAK2 is activated through the steric information transduced through the transmembrane region into the cell. (3,21).…”

Section: The Signaling Mechanism Likely Is Directionally (Orientationmentioning

confidence: 99%

“…Deregulation of JAK2 is thought to be associated with hematopoietic disorders and oncogenesis (2). However, the regulation mechanism of JAK2 remains elusive, and surprisingly little is known about the detailed molecular interactions involved in JAK2 activation processes (3).…”

Section: Introductionmentioning

confidence: 99%

On the Regulation and Activation of JAK2: A Novel Hypothetical Model

2013

Molecular Cancer Research

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show abstract

Regulation of JAKs: Insights Gleaned from the Functional Protein Domains

Cited by 1 publication

References 118 publications

On the Regulation and Activation of JAK2: A Novel Hypothetical Model

On the Regulation and Activation of JAK2: A Novel Hypothetical Model

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