A deficient translocation of CD3zeta, ZAP-70 and Grb2
to lipid raft, as a hallmark of defective adaptive immune response during chronic hepatitis B infection.
Despite the complexity of the protein network associated with stem cell development, the team discovered that restoring the interaction between Grb2
and a protein known as Ptpn11/Shp2 phosphatase was enough to allow stem cells to again change into other cell types.
SH2 domain containing proteins such as growth factor receptor-bound protein 2 (GRB2
), growth factor receptor-bound protein 7 (GRB7), growth factor receptor-bound protein 14 (GRB14), protein tyrosine phosphatase nonreceptor type 11 (SHP-2), and phosphoinositide-3-kinase (PI3K) is recruited and transphosphorylated by TIE2 .
FAK contains various tyrosine-containing motifs which upon phosphorylation interact with other signaling molecules such as srcrelated kinases, PI 3-kinase, the tyrosine phosphatase SHP2, and adaptor proteins Grb2
and Shc .
It also binds to the signalling molecules VAV, GRB2
, P85, NcK, ITK, and FGH through interaction of their SH3 domains with proline motifs in the N-terminal domain of SOCS1 .
Another IGF-1 activated pathway is the rat sarcoma protein /rapidly accelerated Fibrosarcoma kinase (Raf)/mitogen activated protein kinase (MAPK) (also known as Ras-Rafmitogen-activated protein kinase kinase (MEK)-ERK pathway), which, after the binding of IGF-1 to its receptor, induces phosphorylation of tyrosine residues, docking protein such as growth factor receptor-bound protein 2 (GRB2
In the case of ERK, the activation through these receptors leads to the recruitment of downstream effectors including growth factor receptor-bound protein 2 (Grb2
) and protein tyrosine phosphatase non-receptor type 11 (PTPN11/Shp2), leading to the recruitment of Gab1 (GRB2-associated binding protein 1) and SOS (Son of Sevenless).
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).
The lymphoid protein tyros-ine phosphatase Lyp interacts with the adaptor molecule Grb2
and functions as a negative regulator of T cell activation.
In particular, miR-129 has 16 predicted target genes [platelet-derived growth factor receptor, alpha polypeptide (PDGFRA); platelet-derived growth factor receptor, beta polypeptide (PDGFRB); epidermal growth factor receptor (EGFR); phospholipase C, gamma 1 (PLCG1), SHC (Src homology 2 domain containing) transforming protein 4 (SHC4); protein kinase C, alpha (PRKCA); protein kinase C, beta (PRKCB); protein kinase C, delta (PRKCD) protein kinase C, epsilon (PRKCE); protein kinase C, iota (PRKCI); growth factor receptor-bound protein 2 (GRB2
); son of sevenless homolog 1 (SOS1); SOS2; v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS); death-associated protein kinase 1 (DAPK1); DAPK2; DAPK3; and ribosomal protein S6 kinase, 90kDa, polypeptide 5 (RPS6KA5) (also known as MSK1)].