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Atlas of Genetics and Cytogenetics
in Oncology and Haematology
OPEN ACCESS JOURNAL AT INIST-CNRS
Gene Section
Mini Review
PLXNB1 (plexin B1)
José Javier Gómez-Román, Montserrat Nicolas Martínez, Servando Lazuén Fernández, José
Fernando Val-Bernal
Department of Anatomical Pathology, Marques de Valdecilla University Hospital, Medical Faculty,
University of Cantabria, Santander, Spain (JJGR, MN, SL, JFVB)
Published in Atlas Database: March 2009
Online updated version: http://AtlasGeneticsOncology.org/Genes/PLXNB1ID43413ch3p21.html
DOI: 10.4267/2042/44702
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 2.0 France Licence.
© 2010 Atlas of Genetics and Cytogenetics in Oncology and Haematology
Pseudogene
Identity
No.
Other
names:
KIAA0407;
MGC149167;
OTTHUMP00000164806; PLEXIN-B1; PLXN5; SEP
HGNC (Hugo): PLXNB1
Location: 3p21.31
Local order: The Plexin B1 gene is located between
FBXW12 and CCDC51 genes.
Protein
Description
2135 Amino acids (AA). Plexins are receptors for axon
molecular guidance molecules semaphorins. Plexin
signalling is important in pathfinding and patterning of
both neurons and developing blood vessels. Plexin-B1
is a surface cell receptor. When it binds to its ligand
SEMA4D it activates several pathways by binding of
cytoplasmic ligands, like RHOA activation and
subsequent changes of the actin cytoskeleton, axon
guidance, invasive growth and cell migration.
It monomers and heterodimers with PLXNB2 after
proteolytic processing. Binds RAC1 that has been
activated by GTP binding.
It binds PLXNA1 and by similarity ARHGEF11,
ARHGEF12, ERBB2, MET, MST1R, RND1, NRP1
and NRP2.
This family features the C-terminal regions of various
plexins. The cytoplasmic region, which has been called
a SEX domain in some members of this family is
involved in downstream signalling pathways, by
interaction with proteins such as Rac1, RhoD, Rnd1
and other plexins.
Three copies of a cysteine rich repeat are found in
Plexin. The function of the repeat is unknown.
Note
Size: 26,200 bases.
Orientation: minus strand.
DNA/RNA
Description
Functioning gene. 21.00 kb; 37 Exons.
Transcription
7097.00 bp; Number of transcripts: 1; Type:
Messenger.
Two alternatively truncated spliced variant, coding
secreted proteins (lacking the part of the extracellular
domains).
Atlas Genet Cytogenet Oncol Haematol. 2010; 14(3)
Expression
It is highly expressed in fetal kidney, digestive system
(from esophagus to colon), thyroid, prostate and
trachea and at slightly lower levels in fetal brain, lung,
female reproductive system (breast, uterus and ovary)
and liver.
249
PLXNB1 (plexin B1)
Gómez-Román JJ, et al.
Plexin B1 policlonal antibody in foetal human central nervous system. Positive staining in developing neurons.
mutations in the cytoplasmic domain of the PLXNB1
gene in prostate cancer tissue. Mutations were found in
8 (89%) of 9 prostate cancer bone metastases, in 7
(41%) of 17 lymph node meta-stases, and in 41 (46%)
of 89 primary cancers. Forty percent of prostate cancers
contained the same mutation, and the majority of the
primary tumors showed overexpression of the plexinB1 protein. In vitro functional expression studies of the
3 most common mutations showed that the mutant
proteins resulted in increased cell motility, inva-sion,
adhesion, and lamellipodia extension compared to
wildtype. The mutations acted by hindering RAC1 and
RRAS binding and GTP activity.
Localisation
Three isoforms have been identified: The isoform 1 is
located in cell membrane and the isoforms 2 and 3 are
secreted proteins.
Function
Plexin B1 has several molecular functions, like a
receptor activity, transmembrane receptor activity,
protein binding, semaphorin receptor and semaphorin
receptor binding. It is implicated in the next biological
processes: Signal transduction, intracellular signalling
cascade, multicellular organismal development, cell
migration and posi-tive regulation of axonogenesis.
Homology
Implicated in
It belongs to the plexin family and it contains 3
IPT/TIG domains and one Sema domain.
Breast cancer
Prognosis
Loss of protein Plexin B1 expression is associated with
poor outcome in breast cancer ER (estrogen positive)
patients.
Mutations
Somatic
Wong et al. (2007) identified 13 different somatic
Atlas Genet Cytogenet Oncol Haematol. 2010; 14(3)
250
PLXNB1 (plexin B1)
Gómez-Román JJ, et al.
Renal cell carcinoma
Prostate carcinoma
Note
By reverse transcription-polymerase chain reaction
Note
13 somatic missense mutations in the cytoplasmic
domain of the Plexin-B1 gene have been reported.
Mutations were found in cancer bone metastases,
lymph node metastases, and in primary cancers.
Forty percent of prostate cancers contained the same
mutation. Overexpression of the Plexin-B1 protein was
found in the majority of primary tumors. The mutations
hinder Rac and R-Ras binding and R-RasGAP activity,
resulting in an increase in cell motility, invasion,
adhesion, and lamellipodia.
plexin B1 is expressed in nonneoplastic renal tissue,
and it is severely downregulated in clear cell renal
carcinomas. By immunohistochemistry on tissue
microarrays it was shown that plexin B1 protein is
absent in more than 80% of renal cell carcinomas.
Otherwise, all kinds of renal tubules showed strong
membrane reactivity.
When plexin B1 expression is induced with an
expression vector in the renal adenocarcinoma cell line
ACHN, a marked reduction in proliferation rate is
found.
Plexin B1 in normal kidney tissue.
Tubular cortical and medular cells reactive
The same immunostaining after blocking peptide incubation.
Atlas Genet Cytogenet Oncol Haematol. 2010; 14(3)
251
PLXNB1 (plexin B1)
Gómez-Román JJ, et al.
Plexin B1 loss of expression in three cases of renal cell carcinoma (clear cell upper right and left), and papillary (bottom right). One case
of renal clear cell carcinoma with PlexinB1 expression (bottom left).
Osteoarthritis
activation by Plexin-B1 and induces cell contraction in COS-7
cells. J Biol Chem. 2003 Jul 11;278(28):25671-7
Note
Using
semi-quantitative
reverse
transcription
polymerase chain reaction (RT-PCR) analysis, plexin
B1 (PLXNB1) was confirmed to be consis-tently
expressed at lower levels in osteoarthritis.
Disease
Degenerative bone disease.
Usui H, Taniguchi M, Yokomizo T, Shimizu T. Plexin-A1 and
plexin-B1 specifically interact at their cytoplasmic domains.
Biochem Biophys Res Commun. 2003 Jan 24;300(4):927-31
Conrotto P, Corso S, Gamberini S, Comoglio PM, Giordano S.
Interplay between scatter factor receptors and B plexins
controls invasive growth. Oncogene. 2004 Jul 1;23(30):5131-7
Oinuma I, Ishikawa Y, Katoh H, Negishi M. The Semaphorin
4D receptor Plexin-B1 is a GTPase activating protein for RRas. Science. 2004 Aug 6;305(5685):862-5
References
Swiercz JM, Kuner R, Offermanns S. Plexin-B1/RhoGEFmediated RhoA activation involves the receptor tyrosine kinase
ErbB-2. J Cell Biol. 2004 Jun 21;165(6):869-80
Maestrini E, Tamagnone L, Longati P, Cremona O, Gulisano
M, Bione S, Tamanini F, Neel BG, Toniolo D, Comoglio PM. A
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1996 Jan 23;93(2):674-8
Torres-Vázquez J, Gitler AD, Fraser SD, Berk JD, Van N
Pham, Fishman MC, Childs S, Epstein JA, Weinstein BM.
Semaphorin-plexin signaling guides patterning of the
developing vasculature. Dev Cell. 2004 Jul;7(1):117-23
Fujii T, Nakao F, Shibata Y, Shioi G, Kodama E, Fujisawa H,
Takagi S. Caenorhabditis elegans PlexinA, PLX-1, interacts
with transmembrane semaphorins and regulates epidermal
morphogenesis. Development. 2002 May;129(9):2053-63
Basile JR, Afkhami T, Gutkind JS. Semaphorin 4D/plexin-B1
induces endothelial cell migration through the activation of
PYK2, Src, and the phosphatidylinositol 3-kinase-Akt pathway.
Mol Cell Biol. 2005 Aug;25(16):6889-98
Lorenzato A, Olivero M, Patanè S, Rosso E, Oliaro A,
Comoglio PM, Di Renzo MF. Novel somatic mutations of the
MET oncogene in human carcinoma metastases activating cell
motility and invasion. Cancer Res. 2002 Dec 1;62(23):7025-30
Conrotto P, Valdembri D, Corso S, Serini G, Tamagnone L,
Comoglio PM, Bussolino F, Giordano S. Sema4D induces
angiogenesis through Met recruitment by Plexin B1. Blood.
2005 Jun 1;105(11):4321-9
Oinuma I, Katoh H, Harada A, Negishi M. Direct interaction of
Rnd1 with Plexin-B1 regulates PDZ-RhoGEF-mediated Rho
Atlas Genet Cytogenet Oncol Haematol. 2010; 14(3)
252
PLXNB1 (plexin B1)
Gómez-Román JJ, et al.
Basile JR, Gavard J, Gutkind JS. Plexin-B1 utilizes RhoA and
Rho kinase to promote the integrin-dependent activation of Akt
and ERK and endothelial cell motility. J Biol Chem. 2007 Nov
30;282(48):34888-95
B1 and the small GTPase Rac1. J Mol Biol. 2008 Apr
11;377(5):1474-87
Gómez Román JJ, Garay GO, Saenz P, Escuredo K, Sanz
Ibayondo C, Gutkind S, Junquera C, Simón L, Martínez A,
Fernández Luna JL, Val-Bernal JF. Plexin B1 is downregulated
in renal cell carcinomas and modulates cell growth. Transl
Res. 2008 Mar;151(3):134-40
Harduf H, Goldman S, Shalev E. Human uterine epithelial
RL95-2 and HEC-1A cell-line adhesiveness: the role of plexin
B1. Fertil Steril. 2007 Jun;87(6):1419-27
Tong Y, Chugha P, Hota PK, Alviani RS, Li M, Tempel W,
Shen L, Park HW, Buck M. Binding of Rac1, Rnd1, and RhoD
to a novel Rho GTPase interaction motif destabilizes
dimerization of the plexin-B1 effector domain. J Biol Chem.
2007 Dec 21;282(51):37215-24
Swiercz JM, Worzfeld T, Offermanns S. ErbB-2 and met
reciprocally regulate cellular signaling via plexin-B1. J Biol
Chem. 2008 Jan 25;283(4):1893-901
Tong Y, Hota PK, Hamaneh MB, Buck M. Insights into
oncogenic mutations of plexin-B1 based on the solution
structure of the Rho GTPase binding domain. Structure. 2008
Feb;16(2):246-58
Wong OG, Nitkunan T, Oinuma I, Zhou C, Blanc V, Brown RS,
Bott SR, Nariculam J, Box G, Munson P, Constantinou J,
Feneley MR, Klocker H, Eccles SA, Negishi M, Freeman A,
Masters JR, Williamson M. Plexin-B1 mutations in prostate
cancer. Proc Natl Acad Sci U S A. 2007 Nov
27;104(48):19040-5
This article should be referenced as such:
Gómez-Román JJ, Nicolas Martínez M, Lazuén Fernández S,
Val-Bernal JF. PLXNB1 (plexin B1). Atlas Genet Cytogenet
Oncol Haematol. 2010; 14(3):249-253.
Bouguet-Bonnet S, Buck M. Compensatory and long-range
changes in picosecond-nanosecond main-chain dynamics
upon complex formation: 15N relaxation analysis of the free
and bound states of the ubiquitin-like domain of human plexin-
Atlas Genet Cytogenet Oncol Haematol. 2010; 14(3)
253