need an answer for problem 1 question a Problem 1 A certain Receptor Tyrosine Ki
ID: 302880 • Letter: N
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need an answer for problem 1 question a
Problem 1 A certain Receptor Tyrosine Kinase (RTK) si activate G-protein Ras. Activated Ras, in turn, activates the MAP Kinase signaling (Figure 1), which ng pathway utilizes Protein Kinase C (PKC) to promotes cell growth, proliferation, and differentiation. Ras Protein Kinase C MAP Kinase Gene regulatory proteins Cell cycle Transcriptionproteins factors Figure 1. Ras activation of MAP kinase pathway Questions: A. (3 pts) Phorbol esters compounds are structurally similar to diacylglycerols (DAG). Explain why phorbol esters promote tumor growth and development. B. (3 pts) How can the MAP kinase pathway be activated by a G protein-coupled receptor (GPCR) instead of an RTK?Explanation / Answer
Answer (A): Various esters forms of phorbol have the capacity to promote tumor by activating protein kinase C. They do not bind to the ligand site of Protein Kinase C. They bind to some other site and mimic the actions of diacylglycerols (DAG-ligand that activates Protein Kinase C).
The derivatives of Phorbol primarily work by interacting with protein kinase C. The ester part binds to Protein Kinase C exactly the way as natural ligand (diacylglycerol) does and activate the enzyme. Normally, Diacylglycerol degrads quickly in the body. This allow Protein Kinase C to get inactivated by itself. But when ester derivatives of phorbol bind to the Protein Kinase C receptor, they are not degraded efficiently. This activates the Protein Kinase C constitutively. We know that, Protein kinase C is involved in large number of signaling pathways. Therefore, phorbol ester can have a wide range of results, one of which is tumer growth and development .
The main outcome of exposure to ester derivative of Phorbol is tumor promotion. Phorbol is non-carcinogen in itself but it greatly promotes the proliferation of tumor. The key enzyme controlling cell growth and differentiation is Protein Kinase C. When ester group of phorbol binds to Protein Kinase C, cell proliferation pathways in cell are activated. This promotes tumors.
(B): The GPCR are induce a large number of responses including the activation of mitogen-activated protein kinase (MAP kinase) and the extracellular signal-regulated kinases (ERKs). G-proteins singal these receptors. The activation of MAP/ERK kinase induced by G-protein-coupled receptors involves both G-alpha and G-betagamma subunits (Lopez-Ilasaca M, 1998). Activation of MAP kinase through G-betagamma-mediated is mediated by the activation of phosphoinositide 3-kinase, which is followed by a tyrosine phosphorylation, and involve association of the adaptor proteins Shc, Grb2, and Sos. SAPKs/JNKs and p38 are activated by G-betagamma proteins involving Rho family proteins.
GPCRs can activate MAP Kinase pathways RTK independent way as well. Gai -coupled receptors utilize a Gbg-dependent route through phosphatidylinositol-3-kinase. Gaq/11-coupled receptors employ protein kinase C to target calcium or Raf-1 that activates the MAPK.
Reference:
Lopez-Ilasaca M. 1998. Signaling from G-protein-coupled receptors to mitogen-activated protein (MAP)-kinase cascades. Biochem Pharmacol. 56(3):269-77.
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