Cdo Interacts with APPL1 and Activates AKT in Myoblast Differentiation

نویسندگان

  • Gyu-Un Bae
  • Jae-Rin Lee
  • Bok-Geon Kim
  • Ji-Won Han
  • Young-Eun Leem
  • Hey-Jin Lee
  • Seok-Man Ho
  • Myong-Joon Hahn
  • Jong-Sun Kang
چکیده

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.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Cdo Regulates Surface Expression of Kir2.1 K+ Channel in Myoblast Differentiation

A potassium channel Kir2.1-associated membrane hyperpolarization is required for myogenic differentiation. However the molecular regulatory mechanisms modulating Kir2.1 channel activities in early stage of myogenesis are largely unknown. A cell surface protein, Cdo functions as a component of multiprotein cell surface complexes to promote myogenesis. In this study, we report that Cdo forms a co...

متن کامل

Activation of p38α/β MAPK in myogenesis via binding of the scaffold protein JLP to the cell surface protein Cdo

The p38 mitogen-activated protein kinase (MAPK) pathway plays an important role in cell differentiation, but the signaling mechanisms by which it is activated during this process are largely unknown. Cdo is an immunoglobulin superfamily member that functions as a component of multiprotein cell surface complexes to promote myogenesis. In this study, we report that the Cdo intracellular region in...

متن کامل

Phosphorylation of Stim1 at serine 575 via netrin-2/Cdo–activated ERK1/2 is critical for the promyogenic function of Stim1

The promyogenic cell surface molecule Cdo is required for activation of extracellular signal-regulated kinase (ERK) and nuclear factor of activated T cells c3 (NFATc3) induced by netrin-2 in myogenic differentiation. However, the molecular mechanism leading to NFATc3 activation is unknown. Stromal interaction molecule 1 (Stim1), an internal calcium sensor of the endoplasmic reticulum store, pro...

متن کامل

Hypoxia converts the myogenic action of insulin-like growth factors into mitogenic action by differentially regulating multiple signaling pathways.

Insulin-like growth factors (IGFs) stimulate myoblast proliferation and differentiation. It remains elusive how these mutually exclusive cellular responses are elicited by the same growth factor. Here we report that whereas IGF promotes myoblast differentiation under normoxia, it stimulates proliferation under hypoxia. Hypoxia activates the HIF-1 transcriptional program and knockdown of HIF-1al...

متن کامل

KIF5B transports BNIP-2 to regulate p38 mitogen-activated protein kinase activation and myoblast differentiation

The Cdo-p38MAPK (p38 mitogen-activated protein kinase) signaling pathway plays important roles in regulating skeletal myogenesis. During myogenic differentiation, the cell surface receptor Cdo bridges scaffold proteins BNIP-2 and JLP and activates p38MAPK, but the spatial-temporal regulation of this process is largely unknown. We here report that KIF5B, the heavy chain of kinesin-1 motor, is a ...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:

دوره 21  شماره 

صفحات  -

تاریخ انتشار 2010