Sos1 regulates sustained TCR-mediated Erk activation.
The duration and/or the magnitude of Ras-Erk activation are known to be crucial for cell-fate decisions. In T cells, sustained Erk activation correlates with differentiation/proliferation, whereas transient Erk activation parallels with unresponsiveness/apoptosis. The mechanism by which Son of sevenless (Sos) proteins and Ras guanyl-releasing protein 1 (RasGRP1) contribute to dynamics of Erk activation in mature T cells is not yet known. Here, we have assessed this issue using stimuli inducing either transient or sustained TCR signaling and RNA interference mediated suppression of Sos1, Sos2, and RasGRP1 expression in primary human T cells. We found that transient Erk activation depends on RasGRP1 but not on Sos. Conversely, sustained Erk signaling and T-cell activation depend on both Sos1 and RasGRP1. In summary, our data show for the first time that the two guanine nucleotide exchange factors expressed in T cells are differentially involved in the regulation of the duration of Erk phosphorylation and T-cell activation.
Institute of Molecular and Clinical Immunology, Otto-von-Guericke University, Magdeburg, Germany.
Mateusz
M
Poltorak
Ines
I
Meinert
James C
JC
Stone
Burkhart
B
Schraven
Luca
L
Simeoni
D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D004789:Enzyme Activation / Q000502:physiology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D020662:Guanine Nucleotide Exchange Factors / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D006801:Humans; D008213:Lymphocyte Activation / Q000502:physiology*; D020935:MAP Kinase Signaling System / Q000502:physiology*; D008297:Male; D010766:Phosphorylation / Q000502:physiology; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D020837:SOS1 Protein / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D020664:Son of Sevenless Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism
D004268:DNA-Binding Proteins; D020662:Guanine Nucleotide Exchange Factors; C491790:RASGRP1 protein, human; D011948:Receptors, Antigen, T-Cell; D020837:SOS1 Protein; C485509:SOS2 protein, human; D020664:Son of Sevenless Proteins; D048049:Extracellular Signal-Regulated MAP Kinases
Activation kinetics; Ras-Erk activation; RasGRP1; Sos; Sustained signaling