PTBdomaincontaining

PTBdomaincontaining refers to proteins that include the phosphotyrosine-binding (PTB) domain, a modular protein interaction domain that is common in signaling and endocytic adaptor proteins. PTB-containing proteins participate in many cellular processes by linking activated receptors to downstream signaling cascades and by organizing protein complexes at membranes.

The PTB domain is typically about 100 amino acids in length and is found in single or multiple copies within a protein, often alongside other domains such as PH, SH2, or various proline-rich regions. PTB domains generally recognize tyrosine-containing motifs in partner proteins, most famously the NPXY sequence in receptor tails. While some PTB–domain interactions can be influenced by tyrosine phosphorylation, other interactions are independent of phosphorylation, illustrating the domain’s versatile binding modes.

Functional roles of PTB-containing proteins include mediating receptor internalization and trafficking, assembling signaling complexes at the plasma membrane, and transmitting signals from activated receptor tyrosine kinases to downstream pathways. They contribute to diverse pathways such as insulin/IGF signaling, Notch signaling, and neuronal development, often acting as adaptors or scaffolds that coordinate multiple protein interactions.

Notable examples of PTB-containing proteins include IRS1 and IRS2 (insulin receptor substrates), which couple insulin and IGF signaling to downstream effectors; Numb and its relatives, which participate in endocytosis and Notch signaling; DAB1 and DAB2 (Disabled-1 and Disabled-2), which participate in Reelin signaling and endocytosis; and Shc family adapters, which link receptor tyrosine kinases to the Ras/MAPK pathway.

PTB-containing proteins are distributed across metazoans and are studied for their roles in development, metabolism, and disease. See also PTB (phosphotyrosine-binding) domain.