Areas of Interest
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.
Publications
Selected Publications
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.
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.
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.
Wu, Y., Hannigan, M., Kotlyarov, A., Gaestel, M., Wu, D.,
Huang, C-K. (2004) A requirement of MAPKAPK2 in the uropod
localization of PTGN during fMLP-induced neutrophil chemotaxis.
Biochem. Biophys. Res. Commun. 316:666-672.
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 G__-mediated PAK1 and PIX_-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.
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.
Mathews, E.E., Dunn, B. D., Hannigan, M.O., Huang, C-K., and
Lester, E.H. (2002) Genetic control of neutrophil superoxide
burst activity in diabetes resistant Alr/Lt mice Free Radical
Biol and Medicine 32:744-751.
 View more publications, see
Pubmed listing.
rev. 3/09 |
