title: Integrin alphaMbeta2 clustering triggers phosphorylation and activation of protein kinase C delta that regulates transcription factor Foxp1 expression in monocytes.
abstract: Integrins are type I membrane and heterodimeric (alphabeta) cell adhesion receptors. Intracellular signals triggered by ligand-bound integrins are important for cell growth, differentiation, and migration. Integrin alpha(M)beta(2) plays key roles in myeloid cell adhesion, phagocytosis, and degranulation. In this study, we show that protein kinase C (PKC) delta is involved in alpha(M)beta(2) signaling. In human monocytic U937 cells and peripheral blood monocytes, alpha(M)beta(2) clustering induced PKCdelta translocation to the plasma membrane, followed by Tyr(311) phosphorylation and activation of PKCdelta by the src family kinases Hck and Lyn. Interestingly, alpha(M)beta(2)-induced PKCdelta Tyr(311) phosphorylation was not mediated by the tyrosine kinase Syk, which is a well reported kinase in beta(2) integrin signaling. Analysis of the beta(2) cytoplasmic tail showed that the sequence Asn(727)-Ser(734) is important in alpha(M)beta(2)-induced PKCdelta Tyr(311) phosphorylation. It has been shown that alpha(M)beta(2) clustering regulates the expression the transcription factor Foxp1 that has a role in monocyte differentiation. We show that Foxp1 expression was reduced in monocytes that were allowed to adhere to human microvascular endothelial cells. However, the expression of Foxp1 was not affected in monocytes that were treated with PKCdelta-targeting small interfering RNA, suggesting that PKCdelta regulates Foxp1 expression. These results demonstrate a role of PKCdelta in alpha(M)beta(2)-mediated Foxp1 regulation in monocytes.
authors.affiliation: Division of Molecular and Cell Biology, School of Biological Sciences, Nanyang Technological University, Singapore.
authors.forename: Zhi-Hong
authors.initials: ZH
authors.lastname: Xue
authors.forename: Chang-Qing
authors.initials: CQ
authors.lastname: Zhao
authors.forename: Geok-Lin
authors.initials: GL
authors.lastname: Chua
authors.forename: Sze-Wah
authors.initials: SW
authors.lastname: Tan
authors.forename: Xiao-Yan
authors.initials: XY
authors.lastname: Tang
authors.forename: Siew-Cheng
authors.initials: SC
authors.lastname: Wong
authors.forename: Suet-Mien
authors.initials: SM
authors.lastname: Tan
mesh_terms: D002469:Cell Separation; D004789:Enzyme Activation / Q000276:immunology*; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D051858:Forkhead Transcription Factors / Q000096:biosynthesis*; D015870:Gene Expression; D005786:Gene Expression Regulation / Q000276:immunology*; D006801:Humans; D015151:Immunoblotting; D047468:Immunoprecipitation; D019169:Jurkat Cells; D020014:K562 Cells; D016177:Macrophage-1 Antigen / Q000276:immunology / Q000378:metabolism*; D009000:Monocytes / Q000276:immunology / Q000378:metabolism*; D010766:Phosphorylation; D011493:Protein Kinase C / Q000276:immunology / Q000378:metabolism*; D021381:Protein Transport / Q000276:immunology; D012097:Repressor Proteins / Q000096:biosynthesis*; D015398:Signal Transduction / Q000276:immunology; D014162:Transfection; D020298:U937 Cells
chemical_list: C486626:FOXP1 protein, human; D051858:Forkhead Transcription Factors; D016177:Macrophage-1 Antigen; D012097:Repressor Proteins; C087857:protein kinase C gamma; D011493:Protein Kinase C