BIS104 Note9

BIS104 Note9 - Lecture 9 Bio Sci 104 More enzyme-coupled...

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Lecture 9 1 Bio Sci 104 Winter 2010 More enzyme-coupled receptors (control of gene transcription) I. Receptor associated and receptor-like tyrosine phosphatases. A. All processes regulated by protein phosphorylation have two equally accessible regulatory points- kinases and phosphatases. It is the balance between the two, which determines activity of a phosphorylated protein. B. Therefore, cells have also evolved proteins which act as tyrosine phosphatases countering the tyrosine kinases. Some are constitutive (operate to avoid accumulation of phosphorylated- Tyr signals) and others are regulated receptors (e.g. CD45). Found in both soluble and membrane associated forms 1. SHP-1 and SHP-2: soluble tyrosine phosphatases; both have SH2 domains; function in terminating cytokine signaling in blood cells. e.g. SHP terminates cytokine signaling in blood cells by de-phosphorylating Jaks (a receptor associated tyrosine kinase). 2. CD45 - Found on the surface of T and B cells, single pass transmembrane protein with tyrosine phosphatase domain on cytoplasmic side. Normal activating ligands unknown and therefore are called “receptor-like” tyrosine phosphatases. II. Receptors that are serine/threonine kinases A. Example: the TGF-ß receptor . TGF-ß are a family of polypeptide "growth factors" that actually have multiple, and often different effects on a broad spectrum of target cells. Some cell types are stimulated to proliferate by TGF-ßs, some are inhibited. [FYI: TGF-ß belong to a larger family of structurally related proteins which include the activins (involved in mesodermal differentiation in vertebrate development) and the bone morphogenic proteins (which stimulate bone formation)] B. Receptors for TGF-ß are transmembrane proteins with threonine/serine kinase domains. At least one target is called Smads , which are transcription factors that work downstream of TGF- β . C. Overall, somewhat similar concept as Jak/STATs : TGF- β receptors phosphorylate members of the regulated (R-) Smad family. Smads are cytoplasmic in absence of phosphorylation, but once phosphorylated by TGF- β receptors, R-Smads can dimerize with a common Smad 4 partner. This heterodimer now enters the nucleus and turns on, or off, specific genes. Specific genes to be regulated dependent on the identity of the R-Smad. (FYI: There are both activating and inhibitory R-Smads; the latter bind to activated receptors and prevent the positive-acting Smads from being activated.) Note that these phosphorylations take place on serines/threonines not tyrosines as in Jak/STATs .
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Lecture 9 2 III. Supplement to the Jak/STAT system A. The receptor tyrosine kinases regulate a variety of transcription factors mostly indirectly through a multi-step cascade of downstream transducers. B. Some receptor/kniase systems can carry out
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This note was uploaded on 03/02/2010 for the course ECL 242 taught by Professor Holly during the Winter '10 term at UC Davis.

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BIS104 Note9 - Lecture 9 Bio Sci 104 More enzyme-coupled...

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