There are two main IRS proteins
present in our human bodies, and they are IRS1 and IRS2.
White, "IRS proteins
and the common path to diabetes," American Journal of Physiology-Renal Physiology, vol.
The insulin receptor after being activated by binding with insulin promotes the tyrosine phosphorylation of a number of cellular proteins including the IRS proteins
which are major physiological targets of the activated insulin receptor kinase.
Thus, IRS proteins
exert dual function by linking receptor-associated tyrosine kinase activity to cytoplasmic effectors and by bringing together the appropriate signaling molecules .
Zick, "Ser/Thr phosphorylation of IRS proteins
: a molecular basis for insulin resistance," Science's STKE Signal Transduction Knowledge Environment, vol.
White, "Regulating insulin signaling and [beta]-cell function through IRS proteins
," Canadian Journal of Physiology and Pharmacology, vol.
PI3K consists of p85 regulatory and p110 catalytic subunits and becomes an activated enzyme after binding to the phosphorylated IRS proteins
. The activated PI3K catalyzes the production of phosphatidylinositol (3,4,5) triphosphate, which activates the serine kinase Akt by phosphorylation.
The effectors that have been characterized to bind IRS proteins
include phosphatidyl-inositol-3-kinases (PI3K), Growth factor receptor-bound protein 2 (Grb2), SH2 domain-containing tyrosine phosphatase (SHP-2), Fyn, cellular CT10 regulator of kinase (c-Crk), among others, all of which intervene as mediators in metabolic functions and in insulin growth promoter functions (17).
Phosphorylated IRS proteins
act as docking sites for several intracellular proteins such as Grb2, NcK and the regulatory subunit p85 of phosphatidylinositol 3-Kinase (PI3K), which mediate different actions of insulin.
Important signaling molecules downstream of IRS proteins
and Shc include MAPK and PI3K (Saltiel et al., 2001).
The IRS proteins
are cytoplasmic proteins, with multiple tyrosine phosphorylation sites, and phosphorylation of IRS proteins
has been implicated as the first post receptor step in insulin signal transmission.
IR-[beta] tyrosine kinase, when activated by insulin, phosphorylates IRS proteins