Cytokines and their receptors play critical roles in a vast number of physiological functions such as the formation of mature blood cells, the function of the immune system, stem cell maintenance, and metabolism. Binding of cytokines to cytokine receptors triggers conformational changes in receptors dimerization/oligomerization, and results in the activation of cytosolic Janus tyrosine kinases (JAKs). Activated JAK kinases then phosphorylate tyrosine residues on the cytokine receptors, providing docking sites for SH2 domain-containing intracellular signaling proteins. These signaling proteins, including the signal transducers and activators of transcription (STAT) proteins, are then activated and signal transduction cascades are initiated. My laboratory is interested in the molecular mechanisms of cytokine receptor signal transduction, and understanding how deregulation in these mechanisms results in human diseases such as cancer. We use cell biology, molecular biology, and structural biology approaches to study the erythropoietin receptor (EpoR), the thrombopoietin receptor (TpoR), the leptin receptor (LepR), and their associated Janus tyrosine kinase JAK2. Particularly, we focus on three interrelated areas of cytokine receptor signaling: structure of the receptor/JAK complex, JAK regulated receptor trafficking, and regulation of JAK kinase activation.
RESEARCH INTERESTS
Cytokine receptor
Signal transduction
Hematopoiesis
Structure-function analysis of protein
Cancer
RECENT PUBLICATIONS
Constantinescu N. S., Huang L.J., Nam H. S., and Lodish H. F., "The Erythropoietic receptor cytosolic juxtamembrane domain contains an essential, precisely oriented, hydrophobic motif." Molecular Cell, 7:377-385, February 2001
Huang L.J., Constantinescu N. S., and Lodish H. F., "The N-terminal domain of Janus Kinase 2 is required for Golgi processing and cell surface expression of erythropoietin receptor." Molecular Cell, 8:1327-1338, December 2001
Flint-Ashtamker G., Eisen-Lev R., Cohen J., Huang L.J., and Newmann D., "Amino acid residues 268-276 of the erythropoietin receptor contain an endocytosis motif and are required for erythropoietin-mediated proliferation via the receptor." 2002, FEBS Letters 518 (1-3):189-94, April 2002
Tong W, Sulahian R, Gross AW, Hendon N, Lodish HF, and Huang L.J., "The Membrane Proximal Region Of The Thrombopoietin Receptor (TpoR) Confers Its High Surface Expression by JAK2-dependent and independent mechanisms" Journal of Biological Chemistry, 281(50):38930-40, December 2006
Michaely P., Zhao Z., Li W.P., Garuti R., Huang L.J., Hobbs H.H., Cohen J.C., "Identification of a VLDL-induced, FDNPVY-independent internalization mechanism for the LDLR" EMBO Journal, 26(14):3273-82, July 2007
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