Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
, 278 (34), 32471-7

STAT4 Requires the N-terminal Domain for Efficient Phosphorylation


STAT4 Requires the N-terminal Domain for Efficient Phosphorylation

Hua-Chen Chang et al. J Biol Chem.


STAT4 (signal transducer and activator of transcription-4) mediates biological effects in response to interleukin-12 (IL-12). STAT4 has multiple domains that have distinct functions in signaling and gene activation. To characterize the role of the STAT4 N-terminal domain in mediating STAT4 biological function, we have generated STAT4-deficient transgenic mice that express human full-length STAT4 or an N-terminal deletion mutant (Delta N-STAT4) lacking the N-terminal 51 amino acids. Whereas full-length STAT4 rescued IL-12 responsiveness, T lymphocytes expressing the STAT4 N-terminal mutant failed to proliferate in response to IL-12 and had limited Th1 cell development as evidenced by minimal interferon-gamma production. Deletion of the N-terminal domain resulted in failure of STAT4 to be phosphorylated following IL-12 stimulation despite similar phosphorylation of JAK2 and TYK2 in full-length STAT4 and Delta N-STAT4 transgenic T cells. We demonstrate that the lack of phosphorylation in cultured cells is due to reduced efficiency of phosphorylation of Delta N-STAT4 by Janus kinases. These data support a new model wherein the N-terminal domain is required to mediate the phosphorylation of STAT4 in addition to the previously documented role in gene transactivation.

Similar articles

See all similar articles

Cited by 11 PubMed Central articles

See all "Cited by" articles

Publication types

MeSH terms

LinkOut - more resources