BMP receptor1A Presented by Jena Buchan

BMP receptor1A

Presented by Jena Buchan

www.answers.com/topic/bone-morphogenetic-protein-receptor-type-1

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

http://en.wikipedia.org/wiki/TGF_beta_signaling_pathway

BMP (TGF-β)Type II receptorType I receptorSmads

http://radium.no/ebsmeland/?k=ebsmeland/Research%20projects

The entire pathway, extra- and intracellular

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 ligand-binding 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”

• Autosomal dominant inheritance

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”

• Autosomal dominant inheritance

• In colon, stomach, or throughout GI tract (3 types)

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”

• 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

Waite and Eng 2003

http://www.emedicine.com/radio/topic567.htm; Waite and Eng 2003

THE END

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