Explain how signaling through integrins is similar to signaling through RTKs (4 pts)
Focal adhesions are found at the cell membrane where the cytoskeleton interacts with proteins of the extracellular matrix. The clustering of integrins at these sites attracts a large complex of proteins and initiates intracellular signalling processes. Many of the signalling functions of integrins depend on a cytoplasmic nonreceptor protein tyrosine kinase called focal adhesion kinase (FAK). Focal adhesions are often the most prominent sites of tyrosine phosphorylation in cells in culture and FAK is one of the major tyrosine-phosphorylated proteins found in focal adhesions (although it can also associate with conventional signalling receptors). FAK is a protein tyrosine kinase of approximately 125 kDa and comprises of a central catalytic domain flanked by large N- and C-terminal non-catalytic domains. The N-terminal domain presumably directs interactions with integrins and growth factor receptors. The central catalytic kinase domain of FAK shares sequence similarity with other receptor and non-receptor protein tyrosine kinases. The C-terminal region of FAK bears protein interaction sites and a sequence responsible for recruiting FAK to the focal adhesions termed the “FAT” (focal adhesion targeting) sequence. The FAT sequence is responsible for recruiting FAK to the focal adhesions and causes this localization by interacting with talin and paxillin. FAT also mediates signalling through Grb2 via phosphorylated Y925.
The localization of focal adhesion kinase (FAK) to sites of integrin clustering initiates downstream signalling. FAK binds to a number of proteins including PI3K, c-Src, paxillin, talin, and GRAF. It plays an important role in regulation of cell motility, and integrin-mediated activation of MAPK pathways. Tyrosine phosphorylation and activation of FAK accompanies integrin-mediated adhesion. 1) Upon activation, FAK autophosphorylates Tyr397, creating a binding site for the Src homology 2 (SH2) domain of Src or Fyn. 2) The Src kinase then phosphorylates a number of focal adhesion components. The major targets include paxillin and tensin, two cytoskeletal proteins that may also have signalling functions and p130CAS, a docking protein. 3) FAK also combines with, and may activate phosphatidylinositol 3-kinase (PI3K) either directly or through Src kinase. 4) Src phosphorylates FAK at Tyr925, creating a binding site for the complex of the adapter Grb2 and Ras guanosine -triphosphate exchange factor mSOS. 5) This leads to activation of Ras and triggers the downstream kinase cascade of Raf-1, MEK and extracellular signal regulated kinase (ERK).
These interactions link FAK to signalling pathways that modify the cytoskeleton and activate mitogen-activated protein kinase (MAPK) cascades. In addition to activating FAK, some β1 and αv integrins also activate the tyrosine kinase Fyn and, through it, the adapter protein Shc. In this pathway, caveolin-1 appears to function as a membrane adapter, which couples the integrin α subunit to Fyn. Shc is then phosphorylated by Fyn at Tyr317 and combines with the Grb2-mSOS complex leading to activation of Ras and triggering the downstream kinase cascade leading to ERK activation. Although most integrins interact with caveolin-1 and Fyn, only a subset of integrins can activate Fyn and thereby recruit Shc. Integrin engagement has also been reported to directly activate other arms of the MAP kinase pathway including c-Jun kinase (Jnk) and p38 MAPK. Recent evidences suggest that direct signalling through integrins also could be linked to activation of the Rho-related branch of the Ras GTPase superfamily, especially Rho, Rac and CDC42. Members of the Rho-family of small GTPases influence many key cellular processes but are particularly important in regulation of the actin cytoskeleton.
Explain how signaling through integrins is similar to signaling through RTKs (4 pts)
Explain the function of GEFs and GAPs and how one of these is relevant to signaling through RTKs and integrins. (4 pts)
Give a rationale for why RTKs trigger several different signaling pathways (4 pts)
Growth factor signaling through receptor tyrosine kinases (RTKs) results in multiple phenotypic changes. These changes are elicited in part by RTK activation of distinct yet specific intracellular signaling pathways. Describe the mechanism whereby a growth factor leads to the activation of several different yet specific pathways, and how that specificity is achieved. Begin with the growth factor and end with activation of the different intracellular signaling pathways. You must be comprehensive in your answer. Answer in no more than six...
In signaling through the β-adrenergic receptor the same hormone can have different effects on difference cells. Explain what happens to each of the following and what last signaling step is common to all (2 pts each): A. Heart B. Skeletal Muscle C. Smooth muscle Please no cursive handwritting, I cant read cursive.
Explain using simple details and correspoding "ON" "OFF" signals. Describe signaling through the G-protein linked receptor. Be sure to include the details of the receptor the associating G protein and its subunits, and the events in the sequence they occur. Be sure to include the reset for every step that is activated. Describe the signaling pathway that involves cAMP and G proteins. Include how each step is rest. Include dephosphorylation events. Assume involvement of PKA
Activity 4. Receptor signaling pathway A model of a G protein receptor signaling pathway is represented below. Activation of the signaling pathway results in a cell secreting a neurotransmitter through exocytosis. Activated - Activated adenylyl receptor cyclase GTP АТР CAMP Active G protein Protein- kinase A Inactive Active Protein targets Phosphate group A. Different steps in a signaling pathway can amplify the initial signal of one ligand binding to one receptor. Choose one step in the pathway below that results...
4) A signaling pathway proceeds through three protein kinases that are sequentially activated by phosphorylation. In one case, the kinases are held in a signaling complex by a scaffold protein. In the other, the kinases are freely diffusing. Discuss the properties of these two types of organization in terms of the signal amplification, speed, and potential cross talk between signaling pathways. (10 Points)
resistor? 4. Explain why the differential signaling used in the CAN bus is more resistant to problems with the electrical noise in a car than the single-ended signaling used by the other buses.
10 points Hormones work through binding to their specific receptors to induce signaling. Listthe five types of hormone signaling and briefly explain each one * Your answer
6. Explain how human capital theory and signaling theory would answer each of the questions below. You should provide 2 distinct answers for each question. a) What happens to aggregate productivity in a country if more people go to college? (4 points) b) Will employers be willing to pay more for college educated workers vs non-educated workers? (4 points) 6. Explain how human capital theory and signaling theory would answer each of the questions below. You should provide 2 distinct...