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1.
Figure 2.

Figure 2. From: NSP-CAS Protein Complexes.

NSP-CAS signaling networks. The schematic diagram illustrates pathways discussed in the text, depicting how NSP proteins integrate CAS signaling downstream of integrins with signaling pathways downstream of other cell surface receptors. Signaling pathways downstream of cell surface receptors as well as many other known regulators and effectors of CAS family proteins are not shown. Overexpression of several NSP and CAS proteins has been implicated in cancer malignancy and resistance to chemotherapy, which may be due at least in part to perturbation of the signaling interactions shown in the figure.

Yann Wallez, et al. Genes Cancer. 2012 May;3(5-6):382-393.
2.
Figure 1.

Figure 1. From: NSP-CAS Protein Complexes.

Domain structure and phosphorylation sites of CAS and NSP family proteins. Shown are the main isoforms for the various family members and their amino acid lengths. Isoforms of different lengths are shown only for NSP3; the 2 NSP3 shorter isoforms of 702 and 703 amino acids differ from each other in their most amino-terminal segment (indicated in dark gray). CDC25-h = CDC25 homology domain; FAT = focal adhesion–targeting domain (the central serine-rich region of the CAS proteins has the structure of a FAT domain, although it is not commonly designated as such); P/S = proline/serine-rich region; SB = SRC-binding region (containing binding sites for both SRC SH2 and SH3 domains in BCAR1 and EFS and only for the SRC SH2 domain in NEDD9); SH2 = SH2 domain; SH3 = SH3 domain. Phosphorylation sites (Y = tyrosine; S = serine; T = threonine) were obtained from phosphosite.org; the smallest font indicates sites identified by mass spectrometry in >5 samples, the intermediate-sized font indicates sites identified in >50 samples, and the largest font indicates sites identified in >500 samples. It should be noted that identification of phosphorylation sites by mass spectrometry is not necessarily comprehensive. Indicated in gray are the 3 serine phosphorylation sites in the substrate domain of BCAR1 that depend on BCAR3 expression in MDA-MB-231 breast cancer cells94 (the first of which was also detected in >5 other samples), the tyrosine phosphorylated downstream of the EGF receptor in the SH2 domain of NSP1,81 and the tyrosine phosphorylated downstream of the overexpressed EPHB2 receptor in the CDC25 homology domain of NSP3.90

Yann Wallez, et al. Genes Cancer. 2012 May;3(5-6):382-393.
3.
Figure 3.

Figure 3. From: NSP-CAS Protein Complexes.

Conserved interaction domains of NSP and CAS family members enable promiscuous interactions. (A) The NSP CDC25 homology domain is in a “closed” conformation that cannot bind RAS proteins but can tightly interact with CAS proteins. (Left) Structure of the CDC25 homology domain of the active exchange factor SOS bound to its target GTPase, RAS.119 (Middle) The structure of the carboxy-terminal domain of BCAR3 reveals that it also adopts a CDC25 homology domain fold, but in a new closed conformation incapable of RAS binding and exchange factor activity. (Right) The structure of the NSP3-BCAR1 complex reveals that the carboxy-terminal domain of NSP3 also adopts the closed conformation observed for BCAR3. The altered conformation enables strong interaction with the carboxy-terminal FAT domain of the CAS family protein BCAR1 to form an NSP-CAS complex, thus converting the exchange factor domain into an adaptor domain. (B) Surface representations of BCAR1, BCAR3, and NSP3 structures solved by X-ray crystallography,13 and models of NSP1, NEDD9, and EFS. The carboxy-terminus of CASS4 was not modeled due to its greater degree of sequence divergency from the structurally characterized BCAR1. Colors indicate interface residue types identified in the NSP3-BCAR1 complex and the corresponding residues for the other family members. The color coding of interface residues highlights the similarities in the binding interfaces of NSP or CAS family members and thus the potential for promiscuous interactions between the 2 families (with the possible exception of the less conserved CASS4). Arrows indicate experimentally confirmed associations between NSP and CAS family members.

Yann Wallez, et al. Genes Cancer. 2012 May;3(5-6):382-393.

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