Stimulation of tyrosine phosphorylation after ligation of beta7 and beta1 integrins on human B cells.
B lymphocytes express several members of the integrin family of adhesion molecules that mediate cell-cell and cell-extracellular matrix interactions. In addition to beta1 integrins, predominantly alpha4 beta1, mature B cells also express alpha4 beta7, which is a receptor for vascular cell adhesion molecule-1 and fibronectin, and is also involved in the homing of B cells to mucosal sites through binding to a third ligand, mucosal address in cell adhesion molecule-1. Here we describe that crosslinking of alpha4 beta7 integrins on B cell lines and normal tonsillar B cells, induces tyrosine phosphorylation of multiple substrates of 105-130 kD, indicating that beta7 integrin plays a role as signaling molecule in B cells. This pattern of phosphorylated proteins was very similar to that induced following ligation of alpha4 beta1. Interestingly, ligation of alpha5 beta1 or alpha6 beta1 also stimulated the 105-125 kD group of phosphorylated proteins, whereas ligation of beta2 integrins did not. The focal adhesion tyrosine kinase p125FAK was identified as one of these substrates. Beta1 or beta7 mediated tyrosine phosphorylations were markedly decreased when the microfilament assembly was inhibited by cytochalasin B. These results suggest that intracellular signals initiated by different integrins in B cells may converge, to similar cytoskeleton-dependent tyrosine phosphorylated proteins.
Manie
S N
SN
Department of Medicine, Harvard Medical School, Boston, MA, USA.
Astier
A
A
Wang
D
D
Phifer
J S
JS
Chen
J
J
Lazarovits
A I
AI
Morimoto
C
C
Freedman
A S
AS
D000911:Antibodies, Monoclonal / Q000276:immunology; D001402:B-Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D002448:Cell Adhesion / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002460:Cell Line; D003571:Cytochalasin B / Q000494:pharmacology; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D006801:Humans; D039041:Integrin alpha4beta1; D039121:Integrin alpha6beta1; D039641:Integrin beta Chains; D019012:Integrin beta1 / Q000502:physiology*; D016023:Integrins / Q000502:physiology*; D008024:Ligands; D008840:Microfilament Proteins / Q000378:metabolism; D008970:Molecular Weight; D014066:Palatine Tonsil / Q000166:cytology; D010750:Phosphoproteins / Q000096:biosynthesis*; D010766:Phosphorylation / Q000187:drug effects; D019000:Phosphotyrosine / Q000096:biosynthesis*; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011940:Receptor Aggregation; D017469:Receptors, Fibronectin / Q000502:physiology; D016201:Receptors, Lymphocyte Homing / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*
D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules; D039041:Integrin alpha4beta1; D039121:Integrin alpha6beta1; D039641:Integrin beta Chains; D019012:Integrin beta1; D016023:Integrins; D008024:Ligands; D008840:Microfilament Proteins; D010750:Phosphoproteins; D017469:Receptors, Fibronectin; D016201:Receptors, Lymphocyte Homing; C071777:integrin alpha4beta7; C091368:integrin beta7; D019000:Phosphotyrosine; D003571:Cytochalasin B; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496050:PTK2 protein, human