Surfactant Protein A - From Genes to Human Lung Diseases

Heinrich, Stephanie; Hartl, Dominik; Griese, Matthias

doi:10.2174/092986706778773112

Cited by 29 publications

(17 citation statements)

References 139 publications

(193 reference statements)

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“…After vascular injury, tPA stimulates VSMC migration and remodeling of the surrounding extracellular matrix, key features that promote vascular repair. SP-A levels are decreased in the lungs of patients with cystic fibrosis and respiratory distress syndrome, as well as chronic lung diseases (Heinrich et al, 2006), and it is thought that CKAP4 may play a role in SP-A recycling and SP-A signaling by mediating transport of SP-A from the ER to the plasma membrane and/or in SP-A binding at the PM and subsequent internalization (Gupta et al, 2006). Although it is not known whether CKAP4 palmitoylation is required for mediating the effects of tPA in smooth muscle cells or SP-A in type II pneumocytes, the functional significance of CKAP4 palmitoylation in cell membrane localization of CKAP4 and in APF-mediated signaling in IC illustrate the wide-ranging significance of palmitoylation.…”

Section: Discussionmentioning

confidence: 99%

Palmitoylation of Cytoskeleton Associated Protein 4 by DHHC2 Regulates Antiproliferative Factor-mediated Signaling

Planey

Keay

Zhang

et al. 2009

MBoC

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Previously, we identified cytoskeleton-associated protein 4 (CKAP4) as a major substrate of the palmitoyl acyltransferase, DHHC2, using a novel proteomic method called palmitoyl-cysteine identification, capture and analysis (PICA). CKAP4 is a reversibly palmitoylated and phosphorylated protein that links the ER to the cytoskeleton. It is also a high-affinity receptor for antiproliferative factor (APF), a small sialoglycopeptide secreted from bladder epithelial cells of patients with interstitial cystitis (IC). The role of DHHC2-mediated palmitoylation of CKAP4 in the antiproliferative response of HeLa and normal bladder epithelial cells to APF was investigated. Our data show that siRNA-mediated knockdown of DHHC2 and consequent suppression of CKAP4 palmitoylation inhibited the ability of APF to regulate cellular proliferation and blocked APF-induced changes in the expression of E-cadherin, vimentin, and ZO-1 (genes known to play a role in cellular proliferation and tumorigenesis). Immunocytochemistry revealed that CKAP4 palmitoylation by DHHC2 is required for its trafficking from the ER to the plasma membrane and for its nuclear localization. These data suggest an important role for DHHC2-mediated palmitoylation of CKAP4 in IC and in opposing cancer-related cellular behaviors and support the idea that DHHC2 is a tumor suppressor. INTRODUCTIONPalmitoylation is the posttranslational addition of the 16-carbon palmitate group to specific cysteine residues of proteins (Smotrys and Linder, 2004) via a labile thioester bond. Unlike other forms of lipidation, such as myristoylation and prenylation, palmitoylation is reversible which allows for dynamic regulation of protein-membrane interactions, trafficking between membrane compartments (Wedegaertner and Bourne, 1994;Jones et al., 1997;Moran et al., 2001;Zacharias et al., 2002), and synaptic plasticity (el-Husseini Ael and Bredt, 2002). For many years it was believed that palmitoylation occurred primarily by autocatalytic mechanisms (Bizzozero et al., 1987;Bano et al., 1998); however, the recent discovery of a family of palmitoyl acyltransferase (PAT) enzymes that catalyze protein palmitoylation has reversed this notion, expanding the complexity of the mechanisms by which palmitoylation is regulated (Lobo et al., 2002;Roth et al., 2002;Fukata et al., 2004;Linder and Deschenes, 2007).PATs are encoded by the ZDHHC gene family and are characterized by an Asp-His-His-Cys motif (DHHC) within a cysteine-rich domain (CRD). The DHHC and CRD domains are essential for palmitoyl acyltransferase activity (Roth et al., 2002;Fukata et al., 2004;Sharma et al., 2008). Twenty-three genes encoding proteins with DHHC-CRD domains have been identified in mouse and human databases (Fukata et al., 2004). Of these, seven have already been shown to be associated with human disease: DHHC8 with schizophrenia (Mukai et al., 2004); DHHC17/HIP14 with Huntington's disease (Yanai et al., 2006); DHHC15 and DHHC9 with X-linked mental retardation (Mansouri et al., 2005;Raymond et al., 2007); and DHHC2, D...

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Section: Discussionmentioning

confidence: 99%

Palmitoylation of Cytoskeleton Associated Protein 4 by DHHC2 Regulates Antiproliferative Factor-mediated Signaling

Planey

Keay

Zhang

et al. 2009

MBoC

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“…39 In addition to its crucial activity as a lipid stabilizer, SP-A plays important roles in the regulation of local innate inflammatory processes. 40 -42 Reduced intra-alveolar levels of SP-A are associated with several pulmonary diseases, 43,44 and reduced SP-A content and impairment of pulmonary surfactant activity have been demonstrated in LTRs early post-transplant, in relation to ischemia-reperfusion injury. 45 Our results confirm and extend this observation.…”

Section: Discussionmentioning

confidence: 99%

Bronchoalveolar Lavage Fluid Proteome in Bronchiolitis Obliterans Syndrome: Possible Role for Surfactant Protein A in Disease Onset

Meloni

Salvini

Bardoni

et al. 2007

The Journal of Heart and Lung Transplantation

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“…SP-A consists of eight trimers, each of those trimers including a long triple-helical collagenous stem, a flexible hinge, a helical bundle connector and a globular head [19][20][21].…”

Section: Particle Propertiesmentioning

confidence: 99%