Pathways - manually collected, often from reviews:
OpenBEL Selventa BEL large corpus:
IRS4
→
INSR
(directlyIncreases, IRS4 Activity)
Evidence: The insulin receptor, a ligand-stimulated tyrosine kinase, mediates the first steps in insulin action (White and Yenush, 1998). The activated receptor phosphorylates multiple proteins-e.g., insulin receptor substrates (IRS)-1, -2, -3, and -4. Phosphorylation of tyrosine residues in these substrates leads to activation of multiple downstream signaling pathways.
OpenBEL Selventa BEL large corpus:
IRS4
→
INSR
(directlyIncreases, IRS4 Activity)
Evidence: Phosphotyrosine at site 960 of the b subunit just inside the membrane creates an NPXpY-recognition motif for the PTB domain of the IRS proteins. Modification of this tyrosine completely inhibits subsequent phosphorylation of IRS-1 and other insulin receptor substrates and leads to loss of most insulin-dependent biological actions
OpenBEL Selventa BEL large corpus:
IRS4
→
INSR
(directlyIncreases, IRS4 Activity)
Evidence: Insulin receptor substrates are a growing family of proteins that are phosphorylated by the activated insulin receptor. To date, nine members of this family have been identified, including IRS-1 (17, 18), IRS-2 (19), IRS-3 (20), and IRS-4 (21), which are generally viewed as the most specific for insulin signaling; Gab-1 (22); Shc, which has three isoforms (23); and p62dok Following insulin binding, the receptor undergoes autophosphorylation on multiple tyrosine residues. This results in activati...
OpenBEL Selventa BEL large corpus:
IRS4
→
INSR
(directlyIncreases, IRS4 Activity)
Evidence: insulin stimulates the mitogen-activated protein (MAP) kinase extracellular signalregulated kinase (ERK) (Fig. 2). This pathway involves the tyrosine phosphorylation of IRS proteins and/or Shc, which in turn interact with the adapter protein Grb2, recruiting the Son-of-sevenless (SOS) exchange protein to the plasma membrane for activation of Ras.