HPK1 Inhibits AP-1

Abstract

HPK1, a member of the germinal center kinase family, is expressed only in hematopoietic cells. Liou et al. found that T cell receptors (TCRs) and B cell receptors activate HPK1 through similar pathways. In activated T cells, HPK1 activation was dependent on the nonreceptor tyrosine kinases, Lck and ZAP-70, and the adapter proteins, linker for activation of T cells (LAT) and SH2 domain-containing leukocyte protein of 76 kD (SLP-76). In activated B cells, HPK1 activation was dependent on the nonreceptor tyrosine kinases Lyn and Syk, the adapter protein, B cell linker protein (BLNK), and either of the adapter proteins Grb2 or Grap. In transfected cells, HPK1 inhibited AP-1 and extracellular signal-regulated kinase 2 (ERK2) activation by TCR stimulation. The authors suggest that HPK1 acts as a negative regulator of the AP-1 pathway in stimulated T cells. Liou, J., Kiefer, F., Dang, A., Hashimoto, A., Cobb, M.H., Kurosaki, T., and Weiss, A. (2000) HPK1 is activated by lymphocyte antigen receptors and negatively regulates AP-1. Immunity 12 : 399-408. [Online Journal]