黏液高分泌是慢性气道炎症性疾病的重?±硖卣鳌６罐Ⅴ；槐彼酑激酶底物蛋白(myristoylated alanine-rich C kinase substrate， MARCKS)是黏液分泌过程中的关键蛋白。蛋白激酶C或其他激酶、细胞内钙离子浓度、钙调蛋白、纤维型-肌动蛋白、磷脂酰肌醇4，5二磷酸、热休克蛋白70等均可通过MARCKS的桥梁作用，介导气道分泌颗粒的胞内运动和黏蛋白的出胞释放。

Mucous hypersecretion is a predominant phenotype of the chronic airway inflammation.  Myristoylated alanine-rich C kinase substrate (MARCKS) is a key protein in the process of mucus secretion.  MARCKS can mediate the intracellular movement of airway secretory granules (SGs）and mucin (MUC) exocytosis through the interactions with protein kinase C (PKC, or other kinases), intracellular calcium concentration (［Ca2+］i), calmodulin (CaM), fibrous actin (F-actin), phosphatidylinositol 4,5-bisphosphate (PIP2）or heat shock protein (HSP)70.

［1］ Wu WC, Walaas SI, Nairn AC, et al. Calcium/phospholipid regulates phosphorylation of a Mr “87k” substrate protein in brain synaptosomes［J］. Proc Natl Acad Sci USA，1982,79(17):5249.
［2］McLaughlin S, Hangyás-Mihályné G, Zaitseva I, et al. Reversible-through calmodulin-electrostatic interactions between basic residues on proteins and acidic lipids in the plasma membrane［J］. Biochem Soc Symp, 2005, (72):189-198.
［3］Sundaram M, Cook HW, Byers DM. The MARCKS family of phospholipid binding proteins: regulation of phospholipase D and other cellular components［J］. Biochem Cell Biol, 2004, 82(1):191-200.
［4］Arbuzova A, Schmitz AA, Vergères G. Cross-talk unfolded: MARCKS proteins［J］.Biochem J，2002,362(1)：1-12.
［5］Ellena JF, Burnitz MC, Cafiso DS. Location of the myristoylated alanine-rich C-kinase substrate (MARCKS) effector domain in negatively charged phospholipid bicelles［J］. Biophys J, 2003, 85(4): 2442-2448.
［6］Jackson AD. Airway goblet-cell mucus secretion［J］. Trends Pharmacol Sci, 2001,22(1):39-45.
［7］Williams OW, Sharafkhaneh A, Kim V, et al. Airway mucus：from production to secretion［J］.Am J Respir Cell Mol Biol，2006,34(5):527-536.
［8］Larsson C. Protein kinase C and the regulation of the actin cytoskeleton［J］. Cell Signal, 2006, 18(3):276-284.
［9］Adler KB, Li Y. Airway epithelium and mucus：intracellular signaling pathways for gene expression and secretion［J］.Am J Respir Cell Mol Bio1, 2001,25(4):397-400.
［10］Evans GJ, Wilkinson MC, Graham ME, et al. Phosphorylation of cysteine string protein by protein kinase A.Implications for the modulation of exocytosis［J］.J Biol Chem, 2001, 276 (51): 47877-47885.
［11］Park JA, Crews AL, Lampe WR, et al. Protein kinase C delta regulates airway mucin secretion via phosphorylation of MARCKS protein［J］. Am J Pathol, 2007, 171(6):1822-1830.
［12］Abdullah LH, Bundy JT, Ehre C, et al. Mucin secretion and PKC isoforms in SPOC1 goblet cells: diferential activation by purinergic agonist and PMA［J］. Am J Physiol Lung Cell Mol Physiol，2003,285(2): 49-60.
［13］Li Y, Martin LD, Spizz G, et al. MARCKS protein is a key molecule regulating mucin secretion by human airway epithelial cells in vitro［J］.J Biol Chem, 2001, 276(44):40982-40990.
［14］WANG Ke, WEN Fuqiang, XU Dan. Mucus hypersecretion in the airway［J］. Chinese Medical Journal, 2008, 121(7):649-652.
［15］Gallant C, You JY, Sasaki Y, et al. MARCKS is a major PKC-dependent regulator of calmodulin targeting in smooth muscle［J］.J Cell Sci, 2005,118(16):3595-3605.
［16］Nairn AC, Aderem A. Calmodulin and protein kinase C cross-talk: The MARCKS protein is an actin filament and plasma membrane cross-linking protein regulated by protein kinase C phosphorylation and by calmodulin［J］. Ciba Found Symp, 1992,164(3):145-54; discussion 154-161.
［17］Disatnik MH, Boutet SC, Pacio W, et al. The bidirectional translocation of MARCKS between membrane and cytosol regulates integrin-mediated muscle cell spreading［J］. J Cell Sci, 2004, 117(19): 4469-4479.
［18］Toledo A, Arruti C. Actin modulation of a MARCKS phosphorylation site located outside the effector domain［J］. Biochem Biophys Res Commun, 2009, 383(3):353-357.
［19］Park J, Fang S, Crews AL, et al. MARCKS regulation of mucin secretion by airway epithelium in vitro: interaction with chaperones［J］. Am J Respir Cell Mol Biol, 2008,39(1):68-76.
［20］Rogers DF. Physiology of airway mucus secretion and pathophysiology of hypersecretion［J］. Respir Care, 2007, 52(9):1134-1146; discussion 1146-1149.
［21］Rogers DF, Barnes PJ. Treatment of airway mucus hypersecretion［J］. Ann Med, 2006, 38(2):116-125.
［22］Rogers DF. The role of airway secretions in COPD: pathophysiology, epidemiology and pharmacotherapeutic options［J］. COPD,2005, 2(3):341-353.