Targeting the SH2 Domain-Containing Inositol Phosphatase (SHIP) for Therapy

Abstract

SHIP (SH2 domain containing inositol phosphatases) was identified as a 145kDa multi-domain cytosolic protein expressed specifically in hematopoietic cells that negatively regulates cell growth, survival and proliferation. Aberrant SHIP function is associated with many disease pathologies. There are two aspects to SHIP function: the catalytic function mediated by the central catalytic domain and the non-catalytic function mediated by the protein-protein interaction domains of SHIP. Much is known about the catalytic function of SHIP and its role in regulation of growth factor and immune receptor signaling. However, not much is known about the mechanistic details of the non-catalytic functions of SHIP and this is an active area of research. In this review, we discuss the role of SHIP in different cell types of immune system, its role in various diseases and its potential as a therapeutic target. Keywords: SH2 domain, SH3 domain, SHIP, catalytic and non-catalytic function of SHIP, PI3K, SHIP-deficient, innate and adaptive immunity