Growth factor activity

S6K1 (also known as p70S6 kinase) is a serine/ threonine protein kinase which is involved in the regulation of translation by phosphorylating the 40S ribosomal protein S6. Insulin and several growth factors activate the kinase by phosphorylation in a PI 3-kinase dependent and rapamycin-sensitive manner. Phosphorylation of S6 protein leads to the translation of mRNA with a characteristic 5 polypyrimidine sequence motif. 

Gomez, N., and Cohen, P. (1991). Dissection of the protein kinase cascade by which nerve growth factor activates MAP kinases. Nature 353 170-173. 

Morla, A. 0., Schreurs, J.,Miyajima, A., and Wang, J. H. J. (1988). Hematopoietic growth factors activate the tyrosine phosphorylation of distinct sets of proteins in interleukin-3-dependent murine cell lines. Mol. Cell. Biol. 8 2214-2218. 

Uyttenhove, C., Simpson, R.J. and van Snick, J. (1988) Functional and structural characterisation of P40, a mouse glycoprotein with T cell growth factor activity. Proceedings of the National Academy of Sciences USA 85, 6934—6938. 

In contrast, some cytokines (e.g. some CSFs and EPO) appear to be expressed constitutively. In yet other instances cytokines such as PDGF and TGF-P are stored in cytoplasmic granules and can be rapidly released in response to appropriate stimuli. Other cytokines (mainly ones with growth factor activity, e.g. TGF-P, FGF and IL-1) are found bound to the extracellular matrix in connective tissue, bone and skin. These are released, bringing about a biological response upon tissue injury. 

Growth factors activate multiple signal transduction pathways required for survival and differentiation 473... 

Growth factors have been defined as proteins that stimulate cellular proliferation and promote cellular survival. The number of molecules considered to have growth factor activity has been substantially expanded... 

Proteases might also indirectly mediate cancer spread by either activating positive growth factors or inactivating suppressors of metastasis. One of the best examples of a growth factor activated by a protease is beta-TGF by plasmin (L3). There is, however, no evidence at present that beta-TGF is involved in metastasis. 

Sassone-Corsi P, Mizzen CA, Cheung P, Crosio C, Monaco L, Jacquot S, Hanauer A, Allis CD (1999) Requirement of Rsk-2 for epidermal growth factor-activated phosphorylation of histone H3. Science 285(5429) 886-891... 

Atkin CL, Neilands JB (1968) Rhodotorulic Acid, a Diketopiperazine Dihydroxamic Acid with Growth-Factor Activity. I. Isolation and Characterization. Biochemistry 7 3734... 

Cai H, Smola U, Wixler V, Eisenmann-Tappe I, Diaz-Meco MT, Moscat J, Rapp U, Cooper GM (1997) Role of diacylglycerol-regulated protein kinase C isotypes in growth factor activation of the Raf-1 protein kinase. Mol Cell Biol 17 732-741... 

Ohmichi M, Zhu G, Saltiel AR (1993) Nerve growth factor activates calcium-insensitive protein kinase C-epsilon in PC-12 rat pheochromocytoma cells. Biochem J 295 ( Pt 3) 767-772... 

Kendall RL, Thomas KA. Inhibition of vascular endothelial cell growth factor activity by an endogenously encoded soluble receptor. Proc Natl Acad Sci 1993 90(22) 10,705-10,709. 

Fig. 1.57. Model of the regulation of translation by insulin. Insulin ( and other growth factors) activates the Akt kinase pathway (see ch. 10), whose final result is the phosphorylation of 4E-BPl, a regulatory protein of translation initiation. The 4E-BP1 protein inactivates the initation factor eIF-4E by complex formation. eIE-4E is required, together with the proteins eIE-4A and p220, for the binding of the 40S subunit of the ribosome to the cap structure of the mRNA. If the 4E-BP1 protein becomes phosphorylated as a result of insulin-mediated activation of the PI3 kinase/Akt kinase cascade, then eIE-4E is liberated from the inactive eIP-4E 4E-BPl complex and protein biosynthesis can begin.

In the Akt signaling pathway (review Downward, 1998), first an extracellular growth factor activates the corresponding transmembrane receptor (e.g., PGDF receptor, see 8.1). Consequently, tyrosine phosphorylation takes place on the cytoplasmic domain of the receptor. The tyrosine residues serve as docking sites for the SH2 domain of the p85 subimit of the PI3-kinase. The associated translocation of PI3-kinase is synonymous with its activation. The PtdIns(3,4,5)P3 formed binds to the PH domain of the signal protein next in sequence, the Akt kinase, which recruits the latter to the membrane. 

Elastases—1, 2, 3A, 3B (protease E), medullasin Hepatocyte growth factor activator Glandular kallikreins—EGF-binding protein A-C, NGF-y, renin-y, prostate-specific antigen (PSA), and tonin Mite fecal allergen Der pill... 

Fig. 3.3 The ERK/MAP kinase signaling pathway cytokines and growth factors activate tyrosine kinase to which the adaptor protein Grb2 binds. This localizes SOS to plasma membrane. RAS is then activated by SOS. Activated RAS then binds to RAF, which forms a transient membraneanchoring signal. Active RAF kinase phosphorylates MEK. The activated MEK phosphorylates ERK1/ERK2, which also migrates to the nucleus to phosphorylate ELK-1, Etsl/2 and CREB, resulting in the activation and expression of respective genes (see Color Insert)...

Markadieu N, Crutzen R, Blero D, Erneux C, Beauwens R. 2005. Hydrogen peroxide and epidermal growth factor activate phosphatidylinositol 3-kinase and increase sodium transport in A6 cell monolayers. Am J Physiol Renal Physiol 288 F1201-F1212. 

Bartoli, M., Gu, X., Tsai, N. T., Venema, R. C., Brooks, S. E., et al. 2000. Vascular endothelial growth factor activates STAT proteins in aortic endothelial cehs.. /. Biol. Chem. 275 33189-33192. 

Pienimaki, J. et al. Epidermal growth factor activates hyaluronan synthase 2 in epidermal keratinocytes and increases pericellular and intracellular hyaluronan, J. Biol.Chem., 276, 20428, 2001. 

Fig. 4. Schematic model of the mechanisms of oestrogen control of cell proliferation. Three different mechanisms are illustrated. In (1) the interaction of oestrogen (E) with ER leads to increased transcription of genes whose products are directly involved in the control of cell replication. The mechanism illustrated in (2) postulates that oestrogens modulate the production of autocrine growth factors which in turn bind to growth factor receptors at the cell surface and mitogenesis occurs as a consequence of growth factor-activated metabolic pathways. The underlying hypothesis in (3) is that cells are under inhibitory (I) control by undefined molecules in the extracellular fluid and that oestrogens block the effects of these inhibitory molecules.

C4iH680i4NioFe 2HCI. Believed to be a substituted 5-amino-3-hydro-xybenzoylferrioxamine B. Unstable and decomposes to a mixture of compounds with growth factor activity. 

Ushiro, H., and Cohen, S. (1980). Identification of phosphotyrosine as a product of epidermal growth factor-activated protein kinase in A-431 cell membranes. J. Biol. Chem. 255, 8363-8365. 

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