title: Signal transduction pathways in directed migration of human monocytes induced by human growth hormone in vitro.
abstract: The human growth hormone (GH) was shown to modulate leukocyte functions such as stimulating directed migration of human monocytes in vitro. Dimerisation of GH-receptors leads to the activation of various signalling mechanisms. As transduction of GH signals to monocytes is unknown, we investigated GH signalling mechanisms in monocyte migration using a modified Boyden chamber chemotaxis assay. Inhibition of tyrosyl phosphorylation of GH receptor-associated tyrosine kinase by tyrphostin-23 or staurosporine blocked GH-stimulated monocyte migration down to random levels. Furthermore, pre-incubation with effective concentrations of 4B-phorbol-12-myristate-13-acetate (PMA), staurosporine and bisindolylmaleimide I, inhibitors of protein kinase C, significantly decreased GH-induced migration, suggesting that PKC is involved in the signalling cascade. Additionally, phosphatidylinositol 3-kinase and mitogen-activated protein kinase (MAPK) activation seems to be required. This study revealed signalling pathways in monocyte movement toward GH in vitro.
authors.affiliation: Pneumology Service, Department of General Internal Medicine, Faculty of Medicine, University of Innsbruck, Anichstrasse, 35, 6020 Innsbruck, Austria.
authors.forename: C M
authors.initials: CM
authors.lastname: Kähler
authors.forename: A B
authors.initials: AB
authors.lastname: Pischel
authors.forename: T
authors.initials: T
authors.lastname: Haller
authors.forename: C
authors.initials: C
authors.lastname: Meierhofer
authors.forename: A
authors.initials: A
authors.lastname: Djanani
authors.forename: G
authors.initials: G
authors.lastname: Kaufmann
authors.forename: C J
authors.initials: CJ
authors.lastname: Wiedermann
mesh_terms: D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D013006:Growth Hormone / Q000494:pharmacology*; D006801:Humans; D053614:Janus Kinase 2; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009000:Monocytes / Q000187:drug effects / Q000502:physiology*; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins; D011986:Receptors, Somatotropin / Q000819:agonists; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D011518:Proto-Oncogene Proteins; D011986:Receptors, Somatotropin; D009240:N-Formylmethionine Leucyl-Phenylalanine; D013006:Growth Hormone; D019869:Phosphatidylinositol 3-Kinases; D011505:Protein-Tyrosine Kinases; C507924:JAK2 protein, human; D053614:Janus Kinase 2; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D002118:Calcium