Protein phosphorylation is an essential part of the activating
and regulatory processes in the functioning and responses for a
variety of cells. Attention has been paid to protein phosphorylation
in neutrophils because of the importance of this leukocyte in defense
against infection and in a number of allergic and non-allergic tissue-damaging
inflammatory reactions. The ultimate purpose of the proposed investigation
is to identify, isolate and characterize those proteins which are
phosphorylated when neutrophils are stimulated by chemotactic factors,
cytokines and crosslinking of Fc receptors and the respective protein
kinases for which they are responsible. Attempts will be made to
identify the function of phosphorylated proteins, the role that
phosphorylation plays in these respective functions and what role
the proteins and their phosphorylation play in neutrophil stimulus-response
coupling. For these purposes, the following studies are being pursued:
(1) To define the varieties of neutrophil protein kinases (tyrosine
protein kinases, mitogen-activated protein kinase (MAP kinase),
MAP kinase-activated protein kinase 2, calcium/calmodulin-dependent
protein kinase, histone H4 protein kinase, protein kinase C and
others); the regulation and the mechanism of activation of these
kinases and their respective substrates in various subcellular fractions
of neutrophils.
(2) To define the phosphoproteins, the phosphorylation levels of
which are regulated by chemotactic factors (fMet-Leu-Phe), cytokines,
crosslinking of Fc receptors, calcium ionophores and phorbol esters
in intact neutrophils. Attempts will be made to identify and characterize
the molecular components (protein kinases and their substrates)
of the physiologically important phosphorylation system in neutrophils.
Selected Publications:
To search Pubmed for publications by Dr. Huang, please click
here.
- Mathews, C.E., Dunn, B. D., Hannigan, M.O., Huang, C-K., and Leiter, E.H. (2002) Genetic control of neutrophil superoxide burst activity in diabetes resistant Alr/Lt mice Free Radical Biol and Medicine 32:744-751.
- Hannigan, M., Zhan, L., Zhong Li, Ai. Y., Wu, D. and Huang, C-K. (2002) Neutrophils lacking phosphoinositide 3-kinase g show loss of directionality during N-formyl-Met-Leu-Phe-induced chemotaxis. Proc. Natl. Acad. Sci. 99:3603-3608.
- Hannigan, M.O., Huang, C-K., and Wu, D.(2003) Roles of PI3K in neutrophil function. Curr. Topics in Microbiology and Immunology 282:166-175.
- Li, Z., Hannigan, M., Mo, Z., Liu, B., Lu, W., Smrcka, A..V., Wu, G., Liu, M., Huang, C-K. and Wu, D. (2003) Directional sensing requires Gβγ-mediated PAK1 and PIXα-dependent activation of cdc42. Cell 114:215-227.
- Hannigan, M.O., Huang, C-K., and Wu, D.(2003) Roles of PI3K in neutrophil function. Curr. Topics in Microbiology and Immunology 282:166-175.
- Wu, Y., Hannigan, M., Kotlyarov, A., Gaestel, M., Wu, D., and Huang, C-K. (2004) A requirement of MAPKAPK2 in the uropod localization of PTEN during fMLP-induced neutrophil chemotaxis. Biochem. Biophys. Res. Commun. 316:666-672.
- Keisuke, S., Otani, H., Yamamoto, F., Huang, C-K., Maulik, N. and Das, D.K. (2005) MK2-/- gene knockout mouse hearts carry anit-apoptotic signal and are resistant to ischemia reperfusion injury. J. Mol. Cell Cardiology 38:93-77.
- Nagy N, Shiroto K, Malik G, Huang CK, Gaestel M, Abdellatif M, Tosaki A, Maulik N, Das DK. (2007) Ischemic preconditioning involves dual cardio-protective axes with p38MAPK as upstream target. J Mol Cell Cardiology 42:981-990.
- Wu, Y., Zhan, L., Ai, Y., Hannigan, M., Gaestel, M., Huang, C-K., Madri, J. A (2007) MAPKAPK2 Mediated LSP1 Phosphorylation and FMLP-induced Neutrophil Polarization. Biochem. Biophys. Res. Commun. 358:170-175.
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