Cdo interacts with APPL1 and activates Akt in myoblast differentiation.
Cell-cell interactions between muscle precursors are required for myogenic differentiation; however, underlying mechanisms are largely unknown. Promyogenic cell surface protein Cdo functions as a component of multiprotein complexes containing other cell adhesion molecules, Boc, Neogenin and N-cadherin, and mediates some of signals triggered by cell-cell interactions between muscle precursors. Cdo activates p38MAPK via interaction with two scaffold proteins JLP and Bnip-2 to promote myogenesis. p38MAPK and Akt signaling are required for myogenic differentiation and activation of both signaling pathways is crucial for efficient myogenic differentiation. We report here that APPL1, an interacting partner of Akt, forms complexes with Cdo and Boc in differentiating myoblasts. Both Cdo and APPL1 are required for efficient Akt activation during myoblast differentiation. The defective differentiation of Cdo-depleted cells is fully rescued by overexpression of a constitutively active form of Akt, whereas overexpression of APPL1 fails to do so. Taken together, Cdo activates Akt through association with APPL1 during myoblast differentiation, and this complex likely mediates some of the promyogenic effect of cell-cell interaction. The promyogenic function of Cdo involves a coordinated activation of p38MAPK and Akt via association with scaffold proteins, JLP and Bnip-2 for p38MAPK and APPL1 for Akt.
Bae
Gyu-Un
GU
Department of Molecular Cell Biology, Center for Molecular Medicine, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon 440-746, Republic of Korea.
Lee
Jae-Rin
JR
Kim
Bok-Geon
BG
Han
Ji-Won
JW
Leem
Young-Eun
YE
Lee
Hey-Jin
HJ
Ho
Seok-Man
SM
Hahn
Myong-Joon
MJ
Kang
Jong-Sun
JS
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D015820:Cadherins / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000172:deficiency / Q000378:metabolism*; D002454:Cell Differentiation; D002460:Cell Line; D004789:Enzyme Activation; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D024510:Muscle Development; D032446:Myoblasts / Q000166:cytology* / Q000201:enzymology*; D011485:Protein Binding; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*
C464801:APPL1 protein, human; D048868:Adaptor Proteins, Signal Transducing; D000596:Amino Acids; C510733:Appl1 protein, mouse; D015820:Cadherins; C510744:Cdon protein, mouse; D015815:Cell Adhesion Molecules; D008565:Membrane Proteins; C091279:neogenin; D051057:Proto-Oncogene Proteins c-akt