The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Tyrosine-599 of the c-Mpl receptor is required for Shc phosphorylation and the induction of cellular differentiation.

Interaction of thrombopoietin ( TPO) with its receptor, c-Mpl, triggers cell growth and differentiation responses controlling primitive haemopoietic cell production and megakaryocytopoiesis. To examine the important receptor domains and signal transduction pathways involved in these cellular responses, c-Mpl cytoplasmic domain truncation and tyrosine substitution mutants were generated. In the myelomonocytic leukaemia cell lines WEHI3B-D+ and M1, ectopic expression of the wild-type c-Mpl receptor induced TPO-dependent cellular differentiation characterized by increased cell migration through agar and acquisition of the morphology and molecular markers of macrophages. Consistent with the concept that proliferative and differentiation signals emanate from distinct receptor domains, the C-terminal 33 amino acids of c-Mpl were dispensable for a proliferative response in Ba/F3 cells but proved critical for WEHI3B-D+ and M1 differentiation. Finer mapping revealed that substitution of Tyr599 by phenylalanine within this c-Mpl domain was sufficient to abolish the normal differentiation response. Moreover, in contrast to the normal c-Mpl receptor, this same mplY599F mutant was also incapable of stimulating TPO-dependent Shc phosphorylation, the association of Shc with Grb2 or c-Mpl and of inducing c-fos expression. Thus activation of components of the Ras signalling cascade, initiated by interaction of Shc with c-Mpl Tyr599, may play a decisive role in specific differentiation signals emanating from the c-Mpl receptor.[1]


  1. Tyrosine-599 of the c-Mpl receptor is required for Shc phosphorylation and the induction of cellular differentiation. Alexander, W.S., Maurer, A.B., Novak, U., Harrison-Smith, M. EMBO J. (1996) [Pubmed]
WikiGenes - Universities