+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

A natural hepatocyte growth factor/scatter factor autocrine loop in myoblast cells and the effect of the constitutive met kinase activation on myogenic differentiation



A natural hepatocyte growth factor/scatter factor autocrine loop in myoblast cells and the effect of the constitutive met kinase activation on myogenic differentiation



Journal of Cell Biology 137(5): 1057-1068



As a rule, hepatocyte growth factor/scatter factor (HGF/SF) is produced by mesenchymal cells, while its receptor, the tyrosine kinase encoded by the met proto-oncogene, is expressed by the neighboring epithelial cells in a canonical paracrine fashion. In the present work we show that both HGF/SF and met are coexpressed by undifferentiated C2 mouse myoblasts. In growing cells, the autocrine loop is active as the receptor exhibits a constitutive phosphorylation on tyrosine that can be abrogated by exogenously added anti-HGF/SF neutralizing antibodies. The transcription of HGF/SF and met genes is downregulated when myoblasts stop proliferating and differentiate. The coexpression of HGF/SF and met genes is not exclusive to C2 cells since it has been assessed also in other myogenic cell lines and in mouse primary satellite cells, suggesting that HGF/SF could play a role in muscle development through an autocrine way. To analyze the biological effects of HGF/SF receptor activation, we stably expressed the constitutively activated receptor catalytic domain (p65(tpr-met)) in C2 cells. This active kinase determined profound changes in cell shape and inhibited myogenesis at both morphological and biochemical levels. Notably, a complete absence of muscle regulatory markers such as MyoD and myogenin was observed in p65(tpr-met) highly expressing C2 clones. We also studied the effects of the ectopic expression of human isoforms of met receptor (h-met) and of HGF/SF (h-HGF/SF) in stable transfected C2 cells. Single constitutive expression of h-met or h-HGF/SF does not alter substantially the growth and differentiation properties of the myoblast cells, probably because of a species-specific ligand-receptor interaction. A C2 clone expressing simultaneously both h-met and h-HGF/SF is able to grow in soft agar and shows a decrease in myogenic potential comparable to that promoted by p65(tpr-met) kinase. These data indicate that a met kinase signal released from differentiation-dependent control provides a negative stimulus for the onset of myogenic differentiation.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 008049733

Download citation: RISBibTeXText

PMID: 9166406

DOI: 10.2307/1618060


Related references

Creation of an hepatocyte growth factor/scatter factor autocrine loop in carcinoma cells induces invasive properties associated with increased tumorigenicity. Oncogene 9(4): 1091-1099, 1994

Therapeutic potential of hepatocyte growth factor/scatter factor neutralizing antibodies: inhibition of tumor growth in both autocrine and paracrine hepatocyte growth factor/scatter factor:c-Met-driven models of leiomyosarcoma. Molecular Cancer Therapeutics 8(10): 2803-2810, 2009

Hepatocyte growth factor/scatter factor is an autocrine factor for human normal bronchial epithelial and lung carcinoma cells. Cell Growth and Differentiation 4(7): 571-579, 1993

Inactivation of retinoblastoma family proteins by SV40 T antigen results in creation of a hepatocyte growth factor/scatter factor autocrine loop associated with an epithelial-fibroblastoid conversion and invasiveness. Cell Growth and Differentiation 8(2): 165-178, 1997

Hepatocyte growth factor/scatter factor is an autocrine factor expressed by human normal bronchial epithelial and non-small cell lung carcinoma cells. FASEB Journal 7(3-4): A429, 1993

A Hepatocyte Growth Factor (HGF)/receptor autocrine loop regulates constitutive self-renewal of human periodontal ligament cells but reduces sensitivity to exogenous HGF. Journal of Periodontology 77(10): 1723-1730, 2006

Invasiveness and metastasis of NIH 3T3 cells induced by Met-hepatocyte growth factor/scatter factor autocrine stimulation. Proceedings of the National Academy of Sciences of the United States of America 91(11): 4731-4735, 1994

Scatter factor/hepatocyte growth factor (SF/HGF) induces emigration of myogenic cells at interlimb level in vivo. Developmental Biology 179(1): 303-308, 1996

Selective activation of phospholipase C gamma1 and distinct protein kinase C subspecies in intracellular signaling by hepatocyte growth factor/scatter factor in primary cultured rat neocortical cells. Journal of Neurochemistry 71(2): 592-602, 1998

Autocrine hepatocyte growth factor/scatter factor-Met signaling induces transformation and the invasive/metastatic phenotype in C127 cells. Oncogene 13(4): 853-861, 1996

Activation of both MAP kinase and phosphatidylinositide 3-kinase by Ras is required for hepatocyte growth factor/scatter factor-induced adherens junction disassembly. Molecular Biology of the Cell 9(8): 2185-2200, 1998

Pi3 kinase/akt activation, but not map kinase/creb is required for neuroprotection by scatter factor/hepatocyte growth factor and fgf 1 in cerebellar granule neurons. Society for Neuroscience Abstract Viewer and Itinerary Planner : Abstract No 43 5, 2002

Multiple aspects of the phenotype of mammary epithelial cells transformed by expression of activated M-Ras depend on an autocrine mechanism mediated by hepatocyte growth factor/scatter factor. Molecular Cancer Research 2(4): 242-255, 2004

Differential regulation of the phosphoinositide 3-kinase and MAP kinase pathways by hepatocyte growth factor vs. insulin-like growth factor-I in myogenic cells. Experimental Cell Research 297(1): 224-234, 2004

Radioimmunoscintigraphy of tumors autocrine for human met and hepatocyte growth factor/scatter factor. Molecular Imaging 1(1): 56-62, 2002