Abl promotes cadherin-dependent adhesion and signaling in myoblasts.
Cell-cell contact promotes myogenic differentiation but the mechanisms that regulate this phenomenon are not well understood. Cdo (also known as Cdon), an Ig superfamily member, functions as a component of cell surface complexes to promote myogenic differentiation through activation of p38alpha/beta MAP kinase. We recently showed that N-cadherin ligation activated p38alpha/beta in a Cdo-dependent manner, whereas N-cadherin ligation-dependent activation of ERK MAP kinase was not affected by loss of Cdo. The non-receptor tyrosine kinase Abl associates with Cdo during myoblast differentiation and is necessary for full activition of p38alpha/beta during this process. The Abl SH3 domain binds to a PxxP motif in the Cdo intracellular domain, and both these motifs are required for their promyogenic activity. Here we show that Abl is necessary for p38alpha/beta activation initiated by N-cadherin ligation, but in contrast to Cdo, Abl is also required for N-cadherin-dependent ERK activation. Moreover, Abl is required for efficient cadherin-mediated myoblast aggregation via modulation of RhoA-ROCK signaling. Therefore, Abl regulates N-cadherin-mediated p38alpha/beta activation by multiple mechanisms, more generally through regulation of cell-cell adhesion and specifically as a component of Cdo-containing complexes. The role of Cdo as a multifunctional coreceptor with roles in several pathways is also discussed.
Lu
Min
M
Department of Developmental and Regenerative Biology, Mount Sinai School of Medicine, New York, NY, USA.
Krauss
Robert S
RS
D020816:Amino Acid Motifs; D000818:Animals; D015820:Cadherins / Q000378:metabolism*; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation; D051379:Mice; D032446:Myoblasts / Q000378:metabolism*; D011485:Protein Binding; D016315:Proto-Oncogene Proteins c-abl / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D015398:Signal Transduction; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
D015820:Cadherins; C510744:Cdon protein, mouse; D015815:Cell Adhesion Molecules; D034741:RNA, Small Interfering; D016315:Proto-Oncogene Proteins c-abl; D048051:p38 Mitogen-Activated Protein Kinases; D020742:rhoA GTP-Binding Protein