title: Integrin-mediated tyrosine phosphorylation and cytokine message induction in monocytic cells. A possible signaling role for the Syk tyrosine kinase.
abstract: Activation of cytoplasmic tyrosine kinases is an important aspect of signal transduction mediated by integrins. In the human monocytic cell line THP-1, either integrin-dependent cell adhesion to fibronectin or ligation of beta 1 integrins with antibodies causes a rapid and intense tyrosine phosphorylation of two sets of proteins of about 65-75 and 120-125 kDa. In addition, integrin ligation leads to nuclear translocation of the p50 and p65 subunits of the NF-kappa B transcription factor, to activation of a reporter gene driven by a promoter containing NF-kappa B sites, and to increased levels of mRNAs for immediate-early genes, including the cytokine interleukin (IL)-1 beta. The tyrosine kinase inhibitors genistein and herbimycin A block both integrin-mediated tyrosine phosphorylation and increases in IL-1 beta message levels, indicating a causal relationship between the two events. The components tyrosine phosphorylated subsequent to cell adhesion include paxillin, pp125FAK, and the SH2 domain containing tyrosine kinase Syk. In contrast, integrin ligation with antibodies induces tyrosine phosphorylation of Syk but not of FAK or paxillin. In adhering cells, pre-treatment with cytochalasin D suppresses tyrosine phosphorylation of FAK and paxillin but not of Syk, while IL-1 beta message induction is unaffected. These observations indicate that the Syk tyrosine kinase may be an important component of an integrin signaling pathway in monocytic cells, leading to activation of NF-kappa B and to increased levels of cytokine messages.
authors.affiliation: Department of Pharmacology, School of Medicine, University of North Carolina, Chapel Hill 27599, USA.
authors.forename: T H
authors.initials: TH
authors.lastname: Lin
authors.forename: C
authors.initials: C
authors.lastname: Rosales
authors.forename: K
authors.initials: K
authors.lastname: Mondal
authors.forename: J B
authors.initials: JB
authors.lastname: Bolen
authors.forename: S
authors.initials: S
authors.lastname: Haskill
authors.forename: R L
authors.initials: RL
authors.lastname: Juliano
mesh_terms: D016227:Benzoquinones; D002448:Cell Adhesion / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000378:metabolism; D004789:Enzyme Activation; D004792:Enzyme Precursors / Q000037:antagonists & inhibitors / Q000378:metabolism*; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D015972:Gene Expression Regulation, Neoplastic; D017930:Genes, Reporter; D019833:Genistein; D006801:Humans; D007249:Inflammation; D019012:Integrin beta1; D016023:Integrins / Q000378:metabolism*; D007375:Interleukin-1 / Q000096:biosynthesis* / Q000235:genetics; D047908:Intracellular Signaling Peptides and Proteins; D007529:Isoflavones / Q000494:pharmacology; D047029:Lactams, Macrocyclic; D007948:Leukemia, Monocytic, Acute; D009000:Monocytes / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011809:Quinones / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D017828:Rifabutin / Q000031:analogs & derivatives; D015398:Signal Transduction; D000072377:Syk Kinase; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000378:metabolism
chemical_list: D016227:Benzoquinones; D015815:Cell Adhesion Molecules; D004792:Enzyme Precursors; D016326:Extracellular Matrix Proteins; D005353:Fibronectins; D019012:Integrin beta1; D016023:Integrins; D007375:Interleukin-1; D047908:Intracellular Signaling Peptides and Proteins; D007529:Isoflavones; D047029:Lactams, Macrocyclic; D016328:NF-kappa B; D011809:Quinones; D012333:RNA, Messenger; D017828:Rifabutin; D014443:Tyrosine; C020754:herbimycin; D019833:Genistein; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496050:PTK2 protein, human; C000606896:SYK protein, human; D000072377:Syk Kinase