Interactions between hematopoietic progenitor kinase 1 and its adaptor proteins (Review)

Abstract

Hematopoietic progenitor kinase 1(HPK1), also known as mitogen-activated protein kinase kinase kinase kinase 1 is a serine/threonine protein kinase. It is involved in various cellular events, including mitogen-activated protein kinase signaling, nuclear factor-κB signaling, cytokine signaling, cellular proliferation and apoptosis, T cell receptor/B cell receptor signaling and T/B/dendritic cell-mediated immune responses. Therefore, HPK1 has variety of roles in immunity, and is associated with the pathogenesis of autoimmune diseases, cancer, and the inflammatory response. In these cellular and immune events, HPK1 interacts with several adaptor proteins, including caspase recruitment domain family, member 11, hematopoietic cell-specific protein 1, HPK1-interacting protein of 55 kDa, the growth factor receptor-bound protein 2 family, linker for activated T-cells, the SH2 domain-containing leukocyte protein of 76 kDa family, the v-crk avian sarcoma virus CT10 oncogene homolog family, B-cell adaptor molecule of 32 kDa and non-catalytic region of tyrosine kinase adaptor protein. These adaptor proteins can couple HPK1 with various effector molecules, leading to the transmission of upstream signals to downstream targets. They are crucial in regulating the relocation, phosphorylation, activation and functions of HPK1. HPK1 can also phosphorylate certain proteins, consequently modulating their functions. This review aims to describe the adaptor proteins, which interact with HPK1, particularly focusing on their modes of interaction with HPK1, and the effects that these interactions cause.