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The ROR Receptor Family

  • Chapter
Receptor Tyrosine Kinases: Family and Subfamilies

Abstract

The Ror family of receptor tyrosine kinases (RTKs) are originally identified as orphan receptor tyrosine kinases whose tyrosine kinase domains are highly similar to those of the Trk family of RTKs. They exhibit evolutionarily conserved structure in invertebrate and vertebrate, including Caenorhabditis elegans, Drosophila melanogaster, Xenopus laevis, Mus musculus, and Homo sapiens. Their expression patterns are restricted in the developing nervous systems in nematodes and fruit flies, and both Ror1 and Ror2, members of the Ror-family RTKs in mammals, are expressed at high levels during early embryogenesis, implying that the Ror-family RTKs play roles in embryonic development. Indeed, recent studies using Ror1- and Ror2-deficient mice have revealed their crucial roles in embryonic morphogenesis and development of various organs and tissues. Furthermore, both Ror1 and Ror2 have been shown to act as a receptor or co-receptor for Wnt5a to mediate noncanonical Wnt signaling that regulates diverse cellular functions and behaviors, including cellular polarity, migration, and invasion. In this chapter, we will provide a current overview of the Ror-family RTKs, with an emphasis on their expression patterns and roles during development, and their functional significance in human diseases, including developmental anomalies, cancer progression, and inflammation. We will also describe the structure–function relationship of the Ror-family RTKs to show their intriguing functional features.

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Abbreviations

A–P:

Anterior–posterior

aPKC:

Atypical protein kinase C

ARNT:

Arylhydrocarbon receptor nuclear translocator

BDA2:

Brachydactyly type A2

BDB:

Brachydactyly type B

BDC:

Brachydactyly type C

BRI:

Bone morphogenetic protein receptor type I

CAM-1:

CAN abnormal migration 1

CaSR:

Calcium-sensing receptor

CE:

Convergent extension

Chip:

Chromatin-immunoprecipitation

CKIε:

Casein kinase Iε

CLL:

Chronic lymphocytic leukemia

CPZ:

Carboxypeptidase Z

CRD:

Cysteine-rich domain

Cthrc1:

Collagen triple-helix repeat-containing protein 1

Ddr:

Discoidin-like domain receptor

DKK:

Dickkopf

DMZ:

Dorsal marginal zone

DRM:

Detergent-resistant microdomains

DRS:

Dominant form of Robinow syndrome

Dvl:

Dishevelled

ECM:

Extracellular matrix

EF:

Electrical field

EMT:

Epithelial–mesenchymal transition

ER:

Endoplasmic reticulum

ERDA:

ER-associated degradation

ERK1/2:

Extracellular signal-regulated kinase 1 and 2

FLNa:

Filamin A

Fzd:

Frizzled

GAS:

γ-interferon activation sequence

GRK2:

G protein-coupled receptor kinase 2

GSK3:

Glycogen synthase kinase 3

HH-stage:

Hamburger and Hamilton stage

HIF:

Hypoxia-inducible factor

TGF-β:

Transforming growth factor-β

Ig:

Immunoglobulin

IHC:

Inner hair cell

JNK:

c-Jun N-terminal kinase

KD:

Kinase-dead

LD:

LIM domain

LEF:

Lymphoid enhancer factor

MAP3K:

MAP kinase kinase kinase

MMP:

Matrix metalloproteinase

MTOC:

Microtubule-organizing center

MuSK:

Muscle-specific receptor tyrosine kinase

NMJ:

Neuromuscular junction

OHC:

Outer hair cell

PAPC:

Paraxial protocadherin

PC:

Prostate carcinoma

PCP:

Planar cell polarity

PGC:

Primordial germ cell

PRD:

Proline-rich domain

PTA:

Persistent truncus arteriosus

RCC:

Renal cell carcinoma

RRS:

Recessive form of Robinow syndrome

RTK:

Receptor tyrosine kinase

S/TRD:

Serine/threonine-rich domain

SCF:

Stem cell factor

SFK:

Src-family kinase

sFRP:

Secreted Fzd-related protein

Smo:

Smoothened

STAT:

Signal transducer and activator of transcription

TAK1:

TGF-β-activated kinase-1

TCF:

T-cell factor

TCL1:

T-cell leukemia 1

TEP:

Transepithelial potential difference

TK:

Tyrosine kinase

Trk:

Tropomyosin-receptor-kinase

UTR:

Untranslated region, Ser/Thr, serine/threonine

Vangl2:

Vang-like 2

VHL:

von Hippel-Lindau

VSD:

Ventricular septal defect

Wnts:

Wnt-family proteins

WT:

Wild-type

WT1:

Wilms tumor protein 1

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Authors and Affiliations

  1. Department of Physiology and Cell Biology, Graduate School of Medicine, Kobe University, 7-5-1, Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan

    Mitsuharu Endo, Michiru Nishita, Ryosuke Doi, Makoto Hayashi & Yasuhiro Minami

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  1. Mitsuharu Endo
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  2. Michiru Nishita
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  3. Ryosuke Doi
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  4. Makoto Hayashi
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  5. Yasuhiro Minami
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Correspondence to Yasuhiro Minami .

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; Ror1

Receptor at a glance; Ror1

Chromosome location

1p32-p31 (human), 4 49.6 cM (mouse)

Gene Size (bp)

405018 bp (human), 346755 bp (mouse)

Intron/exon numbers

Intron: 8/exon: 9 (human and mouse)

mRNA size (ORF)

3382 bases (ORF: 2814 bases) (human),

3542 bases (ORF: 2814 bases) (mouse)

Amino acid number

937 (human and mouse)

kDa

MW: 104 kDa, SDS-PAGE: 135 kDa

Posttranslational modifications

phosphorylation, glycosylation, ubiquitination

Domains

immunoglobulin-like domain, cysteine-rich domain, kringle domain, tyrosine kinase domain, serine/threonine-rich domain, proline-rich domain

Ligands

Wnt5a (see text for details)

Known dimerizing partners

Ror2

Pathways activated

See text for details

Tissues expressed

See text for details

Human Diseases

malignancy

Knockout Mouse phenotype

See Table 13.1

Receptor at a glance; Ror2

Chromosome location

9q22.31 (human), 13 34.2 cM (mouse)

Gene Size (bp)

227567 bp (human), 176793 bp (mouse)

Intron/exon numbers

Intron: 8/exon: 9 (human and mouse)

mRNA size

4099 bases (ORF: 2832 bases) (human),

3987 bases (ORF: 2835 bases) (mouse)

Amino acid number

943 (human), 944 (mouse)

kDa

MW: 105 kDa, SDS-PAGE: 135 kDa

Posttranslational modifications

phosphorylation, O-sulfonation

Domains

immunoglobulin-like domain, cysteine-rich domain, kringle domain,

tyrosine kinase domain, serine/threonine-rich domain, proline-rich domain

Ligands

Wnt5a (see text for details)

Known dimerizing partners

See Table 13.4

Pathways activated

See text for details

Tissues expressed

See text for details

Human Diseases

autosomal dominant Brachydactyly type B (BDB), autosomal recessive Robinow syndrome (RRS)

Knockout Mouse phenotype

See Table 13.1

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Endo, M., Nishita, M., Doi, R., Hayashi, M., Minami, Y. (2015). The ROR 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_13

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