Nck-2, a Novel Src Homology2/3-containing Adaptor Protein That Interacts with the LIM-only Protein PINCH and Components of Growth Factor Receptor Kinase-signaling Pathways

Many of the protein–protein interactions that are essential for eukaryotic intracellular signal transduction are mediated by protein binding modules including SH2, SH3, and LIM domains. Nck is a SH3- and SH2-containing adaptor protein implicated in coordinating various signaling pathways, including those of growth factor receptors and cell adhesion receptors. We report here the identification, cloning, and characterization of a widely expressed, Nck-related adaptor protein termed Nck-2. Nck-2 comprises primarily three N-terminal SH3 domains and one C-terminal SH2 domain. We show that Nck-2 interacts with PINCH, a LIM-only protein implicated in integrin-linked kinase signaling. The PINCH-Nck-2 interaction is mediated by the fourth LIM domain of PINCH and the third SH3 domain of Nck-2. Furthermore, we show that Nck-2 is capable of recognizing several key components of growth factor receptor kinase-signaling pathways including EGF receptors, PDGF receptor-β, and IRS-1. The association of Nck-2 with EGF receptors was regulated by EGF stimulation and involved largely the SH2 domain of Nck-2, although the SH3 domains of Nck-2 also contributed to the complex formation. The association of Nck-2 with PDGF receptor-β was dependent on PDGF activation and was mediated solely by the SH2 domain of Nck-2. Additionally, we have detected a stable association between Nck-2 and IRS-1 that was mediated primarily via the second and third SH3 domain of Nck-2. Thus, Nck-2 associates with PINCH and components of different growth factor receptor-signaling pathways via distinct mechanisms. Finally, we provide evidence indicating that a fraction of the Nck-2 and/or Nck-1 proteins are associated with the cytoskeleton. These results identify a novel Nck-related SH2- and SH3-domain–containing protein and suggest that it may function as an adaptor protein connecting the growth factor receptor-signaling pathways with the integrin-signaling pathways.

Hið íslenzka bókmenntafélag; söguágrip.

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Radiation pressure confinement, the shock pinch and feasibility of fusion propulsion,

Caption title.

The superfast pinch experiment.

"Prepared for the Air Force Ballistic Missile Division, Headquarters Air Research and Development Command, under Contract AF 04(647)-309, Thermonuclear Propulsion Research."

Transverse pinch oscillations.

"Prepared for the Air Force Ballistic Missile Division, Headquarters Air Research and Development Command, under Contract AF 04 (647-309 Thermonuclear Propulsion Research."

Particle orbits in the static sheet pinch /

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The grip of honor; a story of Paul Jones and the American revolution,

Mode of access: Internet.

Greenes ghost havnting conie-catchers / Wherein is set down, the arte of humouring. The arte of carrying stones. Will. St. lift. Ia. Fost. law. Ned Bro. catch. and Blacke Robins kindnesse. With the conceits of Doctor Pinch-backe a notable makeshift. Ten times more pleasant then anything yet published of this matter ... London, Printed for R. Iackson and I. North, 1602.

Mode of access: Internet.