Focal adhesion kinase negatively regulates Lck function downstream of the T cell antigen receptor.
Focal adhesion kinase (FAK) is a critical regulator of signal transduction in multiple cell types. Although this protein is activated upon TCR engagement, the cellular function that FAK plays in mature human T cells is unknown. By suppressing the function of FAK, we revealed that FAK inhibits TCR-mediated signaling by recruiting C-terminal Src kinase to the membrane and/or receptor complex following TCR activation. Thus, in the absence of FAK, the inhibitory phosphorylation of Lck and/or Fyn is impaired. Together, these data highlight a novel role for FAK as a negative regulator TCR function in human T cells. These results also suggest that changes in FAK expression could modulate sensitivity to TCR stimulation and contribute to the progression of T cell malignancies and autoimmune diseases.
Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, IA 52242.
Nicole M
NM
Chapman
Sean F
SF
Connolly
Erin L
EL
Reinl
Jon C D
JC
Houtman
D000293:Adolescent; D000328:Adult; D019943:Amino Acid Substitution; D015496:CD4-Positive T-Lymphocytes / Q000201:enzymology; D000081247:CSK Tyrosine-Protein Kinase; D004789:Enzyme Activation / Q000502:physiology; D005260:Female; D051417:Focal Adhesion Kinase 1 / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D006801:Humans; D019169:Jurkat Cells; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000235:genetics / Q000502:physiology*; D008297:Male; D035683:MicroRNAs / Q000235:genetics; D008875:Middle Aged; D009097:Multienzyme Complexes; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000502:physiology; D011499:Protein Processing, Post-Translational; D021381:Protein Transport; D051076:Proto-Oncogene Proteins c-fyn / Q000502:physiology; D034622:RNA Interference; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology*; D014162:Transfection; D055815:Young Adult; D019061:src-Family Kinases / Q000378:metabolism
D035683:MicroRNAs; D009097:Multienzyme Complexes; D011948:Receptors, Antigen, T-Cell; D011993:Recombinant Fusion Proteins; D019000:Phosphotyrosine; D000081247:CSK Tyrosine-Protein Kinase; C494957:FYN protein, human; D051417:Focal Adhesion Kinase 1; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); C496050:PTK2 protein, human; D051076:Proto-Oncogene Proteins c-fyn; D019061:src-Family Kinases; C000631346:CSK protein, human