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The NOK Receptor Family

  • Chapter
Receptor Tyrosine Kinases: Family and Subfamilies

Abstract

The novel oncogene with kinase domain (NOK) is believed to be a typical receptor “pseudokinase” because of its lack of Asp-Phe-Gly (DFG) motif and therefore is unable to transfer phosphate group to the substrate. However, functional analysis demonstrates that NOK is a potent oncogene that could induce cellular transformation, tumorigenesis, and metastasis. Mechanism studies reveal that NOK activates multiple mitogenic signaling pathways such as Ras/MAPK, PI3K/Akt, STAT1, STAT3, and STAT5 signaling pathways. The pleiotropy of NOK oncogene is represented by its ability to directly and physically interact with and subsequently activate a broad and diverse important signaling molecules. On the other hand, NOK also harbors multiple autoinhibitory elements that provide its own with the fine adjustment ability to control the activation strength of downstream signaling cascades. Another level of control that may contribute to NOK-mediated oncogenicity is its self-aggregation ability by forming homo-dimmer and homo-oligomer in which the activated state of NOK could be further enhanced. More importantly, it has been shown recently that NOK might be among the few genes uniquely expressed in the innate and activated NK cells. Examination on patient samples indicates that NOK may have diagnostic, prognostic, or therapeutic values in many types of human cancers, including breast cancer, lung cancer, ovarian cancer, acute leukemia, and prostate cancer. Although significant works have been achieved in the past, understanding on NOK-mediated physiological and pathological functions is still in its infancy and needed to be further unveiled.

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Abbreviations

CDK:

Cyclin-dependent kinases

CNPC:

Castration-naïve prostate cancer

CRPC:

Castration-resistant prostate cancer

DFG:

Asp-Phe-Gly

EGFR:

Epidermal growth factor receptor

EPOR:

Erythropoietin receptor

ERα:

Estrogen receptor-alpha

ERK1/2:

Extracellular signal-regulated kinases 1/2 (ERK1/2)

GSK-3β:

Glycogen synthase kinase-3 beta

H&E staining:

Hematoxylin-eosin staining

JAK:

Janus kinase

NKT:

Natural killer T cells

NOK:

Novel oncogene with kinase domain

PC:

Prostate cancer

PI3K:

Phosphoinositide 3 kinase

RAS/MAPK:

Ras/mitogen-activated protein kinase (MAPK) pathway

RPTK:

Receptor protein tyrosine kinase

Serine/threonine-specific kinase:

Akt

STAT:

Signal transducers and activators of transcription

STYK1:

Serine/threonine/tyrosine kinase 1

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Acknowledgment

The work is supported by National Natural Science Foundation of China (grant No. 30871283 and 81171944).

Author information

Authors and Affiliations

  1. Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College, #5 Dong Dan San Tiao, Beijing, 100005, China

    Li Liu

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  1. Li Liu
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Correspondence to Li Liu .

Editor information

Editors and Affiliations

  1. School of Medicine and Public Health Department of Human Oncology, University of Wisconsin, Madison, Wisconsin, USA

    Deric L. Wheeler

  2. Department of Biological Regulation, Rehovot, Israel

    Yosef Yarden

Receptor at a glance: NOK

Receptor at a glance: NOK

Chromosome location

Chromosome 12p13.2

Gene size (bp)

1,269

Intron/exon number

10/11

Amino acid number

422

KDa

46.4

Posttranslational modifications

Phosphorylation, N-glycosylation, ubiquitination, and myristoylation

Domains

Tyrosine kinase domain, transmembrane domain

Ligands

None

Known dimerizing partners

Homodimer and homotrimer

Pathways activated

RAS/MAPK, PI3K/Akt, STATs

Tissue expressed

Highly expressed in prostate; moderately expressed in the colon, brain, and placenta; can be detected in some cancer cell lines such as hepatoma cells LO2, cervix carcinoma cells HeLa, ovary cancer cells Ho8910 and chronic myelogenous leukemia cells K562; but not be detected in other cancer cell lines such as macrophage/monocyte lineages (U937, Ana-1, and HL-60) and human epidermoid carcinoma A431. Undetectable in most normal lung tissues, widely expressed in lung cancers. Uniquely expressed in the resting and activated NK cells

Human diseases

Breast cancer, lung cancer, ovarian cancer, acute leukemia, prostate cancer, and colorectal cancer

Knockout mouse phenotype

Not known

Cellular localization

Cytoplasm

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Liu, L. (2015). The NOK Receptor Family. In: Wheeler, D., Yarden, Y. (eds) Receptor Tyrosine Kinases: Family and Subfamilies. Springer, Cham. https://doi.org/10.1007/978-3-319-11888-8_19

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