Direct interaction between the cytoplasmic tail of ADAM 12 and the Src homology 3 domain of p85alpha activates phosphatidylinositol 3-kinase in C2C12 cells

The Journal of Biological Chemistry
Qing KangAnna Zolkiewska

Abstract

ADAM 12, a member of the ADAM family of transmembrane metalloprotease-disintegrins, has been implicated previously in the differentiation of skeletal myoblasts. In the present study, we show that the cytoplasmic tail of mouse ADAM 12 interacts in vitro and in vivo with the Src homology 3 domain of the p85alpha regulatory subunit of phosphatidylinositol (PI) 3-kinase. By site-directed mutagenesis, we have identified three p85alpha-binding sites in ADAM 12 involving PXXP motifs located at amino acids 825-828, 833-836, and 884-887. Using green fluorescent protein (GFP)-pleckstrin homology (PH) domain fusion protein as a probe for PI 3-kinase lipid products, we have further demonstrated that expression of ADAM 12 in C2C12 cells resulted in translocation of GFP-PH to the plasma membrane. This suggests that transmembrane ADAM 12, by providing docking sites for the Src homology 3 domain of p85alpha, activates PI 3-kinase by mediating its recruitment to the membrane. Because PI 3-kinase is critical for terminal differentiation of myoblasts, and because expression of ADAM 12 is up-regulated at the onset of the differentiation process, ADAM 12-mediated activation may constitute one of the regulatory mechanisms for PI 3-kinase during myob...Continue Reading

References

Nov 21, 1995·Proceedings of the National Academy of Sciences of the United States of America·R J RicklesM J Zoller
Oct 19, 1995·Nature·T Yagami-HiromasaA Fujisawa-Sehara
May 10, 1996·The Journal of Biological Chemistry·C E Stewart, P Rotwein
Aug 9, 1996·The Journal of Biological Chemistry·P KalimanA Zorzano
Oct 1, 1996·The Journal of Cell Biology·J C EngertN Rosenthal
Oct 1, 1996·Endocrine Reviews·J R FloriniS A Coolican
Feb 7, 1998·The Journal of Biological Chemistry·B J GilpinU M Wewer
Jun 27, 1998·The Journal of Biological Chemistry·F LoechelU M Wewer
Oct 6, 1998·Annual Review of Biochemistry·D A FrumanL C Cantley
Nov 18, 1998·Current Opinion in Cell Biology·R A Black, J M White
Nov 25, 1998·Proceedings of the National Academy of Sciences of the United States of America·B H JiangP K Vogt
Dec 5, 1998·Biochimica Et Biophysica Acta·M P Wymann, L Pirola
Apr 21, 1999·Current Opinion in Cell Biology·S J LeeversM D Waterfield
May 1, 1999·The Journal of Biological Chemistry·F LoechelU M Wewer
May 18, 1999·The American Journal of Pathology·K IbaU M Wewer
Dec 2, 1999·Experimental Cell Research·B Vanhaesebroeck, M D Waterfield
Apr 11, 2000·Molecular and Cellular Biology·M A LawlorP Rotwein
Aug 31, 2000·Biochemical and Biophysical Research Communications·S HougaardU M Wewer
Dec 29, 2000·Journal of Muscle Research and Cell Motility·A BornemanA Fujisawa-Sehara

❮ Previous
Next ❯

Citations

Oct 30, 2012·The Journal of Biological Chemistry·Annelize Z B AragãoAdriana F Paes Leme
Dec 4, 2002·The Journal of Cell Biology·Katherine M SmithDouglas W DeSimone
Dec 3, 2004·Molecular Biology of the Cell·Peggy LafusteFrançois-Jérôme Authier
Jan 9, 2004·Reproductive Biology and Endocrinology : RB&E·DeannaLee M Beauvais, Alan C Rapraeger
Feb 1, 2006·Proceedings of the National Academy of Sciences of the United States of America·Fumihiko FuruyaSheue-yann Cheng
Oct 9, 2008·Seminars in Cell & Developmental Biology·Gillian Murphy
Mar 18, 2008·The International Journal of Biochemistry & Cell Biology·Marie KveiborgUlla M Wewer
Dec 25, 2013·PloS One·Rebecca L RossMargaret A Knowles
Sep 15, 2004·The Journal of Biological Chemistry·Christina SundbergUlla M Wewer
Feb 5, 2008·International Journal of Cancer. Journal International Du Cancer·Emilia DyczynskaAnna Zolkiewska
Dec 14, 2001·The Journal of Biological Chemistry·Zaruhi PoghosyanDylan R Edwards
May 10, 2002·The Journal of Biological Chemistry·Yi CaoAnna Zolkiewska
Feb 19, 2004·The Journal of Biological Chemistry·Daniel V BaxMartin J Humphries
Mar 5, 2003·The Journal of Biological Chemistry·Clare L AbramSara A Courtneidge
Jul 20, 2019·Cells·Natacha Malu Miranda da CostaJoão de Jesus Viana Pinheiro
Feb 26, 2008·Molecular Cancer Research : MCR·Julia L ZhongDylan R Edwards
Jul 29, 2004·The Journal of Biological Chemistry·Motonari TanakaShigeki Higashiyama
Jul 10, 2004·Experimental Cell Research·Zhefeng ZhaoAnna Zolkiewska
Jan 7, 2003·Genes & Development·Darren F Seals, Sara A Courtneidge

❮ Previous
Next ❯

Related Concepts

Related Feeds

AKT Pathway

This feed focuses on the AKT serine/threonine kinase, which is an important signaling pathway involved in processes such as glucose metabolism and cell survival.

ASBMB Publications

The American Society for Biochemistry and Molecular Biology (ASBMB) includes the Journal of Biological Chemistry, Molecular & Cellular Proteomics, and the Journal of Lipid Research. Discover the latest research from ASBMB here.