Download BMP receptor1A - UNC

BMP receptor1A
www.answers.com/topic/bone-morphogenetic-protein-receptor-type-1
Presented by Jena Buchan
Let’s start with the basics
• BMP=bone morphogenetic protein
• receptor1A=version of Type I receptor (also
have 1B and Type II receptors)
• Other names: ALK3, CD292, ACVRLK3
Examining the protein on a cellular
level...
• Transmembrane receptor that links
external BMPs and internal SMAD
proteins
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=657
Examining the protein on a cellular
level...
• Transmembrane receptor that links
external BMPs and internal SMAD
proteins
• Ligands member of TGF-β superfamily
BMPR1A binds BMP2 and BMP4
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=657
Examining the protein on a cellular
level...
• Transmembrane receptor that links
external BMPs and internal SMAD
proteins
• Ligands member of TGF-β superfamily
BMPR1A binds BMP2 and BMP4
• Serine/threonine kinase
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=657
Examining the protein on a cellular
level...
• Transmembrane receptor that links
external BMPs and internal SMAD
proteins
• Ligands member of TGF-β superfamily
BMPR1A binds BMP2 and BMP4
• Serine/threonine kinase
• Activation requires Type II receptor
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=657
Signaling Pathway

BMP (TGF-β)Type II receptorType I receptorSmads
http://en.wikipedia.org/wiki/TGF_beta_signaling_pathway
The entire pathway, extra- and intracellular
http://radium.no/ebsmeland/?k=ebsmeland/Research%20projects
Now, its biological role in the
organism...
• Tumor suppressor located on chromosome 10q23
www.genecards.org/cgi-bin/carddisp.pl?gene=BMPR1A
Now, its biological role in the
organism...
• Tumor suppressor located on chromosome 10q23
www.genecards.org/cgi-bin/carddisp.pl?gene=BMPR1A
•
Studies in Xenopus and chick embryos
~role in establishing vertebral body plan
~differentiation of all 3 germ layers
*includes activities like adipocyte and
chondrocyte differentiation
http://www2.hu-berlin.de/biologie/zoologie/sammlung/Tafeln/Onto%20I.html
• Studies in mice embryos
~embryonic lethal/required for gastrulation
~necessary for correct germ layer
morphogenesis
Davis, S., Miura, S., Hill, C., Mishina, Y. and Klingensmith, J. (2004). BMP receptor IA is required in the mammalian embryo for
endodermal morphogenesis and ectodermal patterning. Dev. Biol. 270, 47-63.
• Even more from mice...
~intestinal development
inhibits stem cell
self-renewal through
Wnt-β-catenin path
(He et. al. 2004)
www.bioscience.org/1999/v4/d/beaulieu/fulltext.htm
And now...
BMPR1A & CANCER
The cancer precursor...
• BMPR1A mutations associated with 20-25% of juvenile
polyposis syndrome (JPS) cases
The cancer precursor...
• BMPR1A mutations associated with 20-25% of juvenile
polyposis syndrome (JPS) cases
• Truncating, in ligand-binding and kinase domains
Waite and Eng 2003
The cancer precursor...
• BMPR1A mutations associated with 20-25% of juvenile
polyposis syndrome (JPS) cases
• Truncating, in ligand-binding and kinase domains
• Some missense mutations, likely result in loss of ligandbinding or kinase activity
• JPS type of inherited hamartomatous polyposis
syndrome
– Hamartomatous polyps=
“benign...outgrowths in the GI tract,
which comprise at least 2 components
of the normal intestine but in
developmentally incorrect apposition”
Waite and Eng 2003
• JPS type of inherited hamartomatous polyposis
syndrome
– Hamartomatous polyps=
“benign...outgrowths in the GI tract,
which comprise at least 2 components
of the normal intestine but in
developmentally incorrect apposition”
Waite and Eng 2003
• Autosomal dominant inheritance
• JPS type of inherited hamartomatous polyposis
syndrome
– Hamartomatous polyps=
“benign...outgrowths in the GI tract,
which comprise at least 2 components
of the normal intestine but in
developmentally incorrect apposition”
Waite and Eng 2003
• Autosomal dominant inheritance
• In colon, stomach, or throughout GI tract (3 types)
• JPS type of inherited hamartomatous polyposis
syndrome
– Hamartomatous polyps=
“benign...outgrowths in the GI tract,
which comprise at least 2 components
of the normal intestine but in
developmentally incorrect apposition”
Waite and Eng 2003
• Autosomal dominant inheritance
• In colon, stomach, or throughout GI tract (3 types)
• JPS= ↑ risk for gastrointestinal cancers (estimates
range from 10-50%)
– Colon/colorectal most common; also see gastric,
small intestine, and pancreatic cancers
http://www.emedicine.com/radio/topic567.htm; Waite and Eng 2003
THE END
(Go Women’s Bball!)
Questions, comments, etc.?