1. BMP receptor1A Presented by Jena Buchan www.answers.com/topic/bone-morphogenetic-protein-receptor-type-1

2. 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

3. 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

4. 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

5. 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

6. 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

7. Signaling Pathway http://en.wikipedia.org/wiki/TGF_beta_signaling_pathway  BMP (TGF-β)  Type II receptor  Type I receptor  Smads

8. http://radium.no/ebsmeland/?k=ebsmeland/Research%20projects The entire pathway, extra- and intracellular

9. Now, its biological role in the organism... Tumor suppressor located on chromosome 10q23 www.genecards.org/cgi-bin/carddisp.pl?gene=BMPR1A

10. 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

11. 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.

12. 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

13. And now... BMPR1A & CANCER

14. The cancer precursor... BMPR1A mutations associated with 20-25% of juvenile polyposis syndrome (JPS) cases

15. 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

16. 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

17. 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

18. 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

19. 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

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

21. THE END Questions, comments, etc.? (Go Women’s Bball!)