Stimulation of TK1 lymphoma cells via alpha 4 beta 7 integrin results in activation of src-tyrosine- and MAP-kinases.
The lymphocyte integrin alpha 4 beta 7 is a cell surface adhesion receptor involved in initiating lymphocyte homing to gut-associated/mucosal lymphoid tissues by binding the mucosal addressin cell adhesion molecule-1 (MAdCAM-1). Other known ligands are vascular cell adhesion molecule-1, fibronectin, and the alpha 4 integrin chain itself. Here, we demonstrate that stimulation of the alpha 4 beta 7 integrin through its alpha 4 subunit (mAb R1-2), beta 7 subunit (mAb M293), or the combinatory epitope (mAb DATK32) enhances tyrosine phosphorylation of several cellular proteins in the murine TK1 lymphoma cell line. The two src-kinases p56lck and p59fyn were identified as possible mediators and substrates of the detected tyrosine phosphorylation. Furthermore, we observed activation of the MAP-kinases ERK1/2.
Uhlemann
A C
AC
Department of Physiology, University of Tuebingen, Germany.
Brenner
B
B
Gulbins
E
E
Linderkamp
O
O
Lang
F
F
D000818:Animals; D000081247:CSK Tyrosine-Protein Kinase; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D015815:Cell Adhesion Molecules; D004789:Enzyme Activation; D007136:Immunoglobulins / Q000378:metabolism; D016023:Integrins / Q000378:metabolism*; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000378:metabolism; D008223:Lymphoma; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D009088:Mucoproteins / Q000378:metabolism; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051076:Proto-Oncogene Proteins c-fyn; D016201:Receptors, Lymphocyte Homing / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000378:metabolism; D019061:src-Family Kinases
D015815:Cell Adhesion Molecules; D007136:Immunoglobulins; D016023:Integrins; C489082:Madcam1 protein, mouse; D009088:Mucoproteins; D011518:Proto-Oncogene Proteins; D016201:Receptors, Lymphocyte Homing; C071777:integrin alpha4beta7; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; D000081247:CSK Tyrosine-Protein Kinase; C494960:Fyn protein, mouse; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D051076:Proto-Oncogene Proteins c-fyn; D019061:src-Family Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases