Receptors with serine/threonine kinase activity

TGF-/3, a factor, unrelated to TGF- which binds to a receptor with serine/threonine kinase activity. 

B. Receptors with serine/ threonine kinase activity... 

Other kinase receptors are serine/threonine kinases, protein kinases, and mitogen-activated protein (MAP) kinases. Insulin, transforming growth factor-beta (TGF- 8), and platelet-derived growth factor (PDGF) are the natural ligands that interact with kinase receptors. 

Cordes N, Frick S, Brunner TB et al (2007) Human pancreatic tumor cells are sensitized to ionizing radiation by knockdown of caveolin-1. Oncogene 26 6851-6862 Couet J, Sargiacomo M, Lisanti MP (1997) Interaction of a receptor tyrosine kinase, EGF-R, with caveolins. Caveolin binding negatively regulates tyrosine and serine/threonine kinase activities. J Biol Chem 272 30429-30438 Coussens LM, Werb Z (2002) Inflammation and cancer. Nature 420 860-867... 

BMPs interact with BMP receptors I and II on the cell surface/membrane [1,22]. BMP receptors are serine/threonine kinases. The intracellular substrates for these kinases called Smads function as relays to activate the transcriptional machinery [23]. The three functional classes are (1) receptor-regulated Smads, namely, Smads 1, 5, and 8, (2) the common partner Smad — 4, and (3) the inhibitory Smads 6 and 7. There are Smad-dependent and independent pathways for activation of BMP signaling including new bone formation. 

Figure 3. MAP kinase regulatory pathway. The MAP kinase signaling pathway begins with activation of the receptor tyrosine kinase (RTK) by exogenous signals, such as growth factors and insulin. The signal is then transmitted into the cell via activation of the Raf serine/threonine kinase either directly by the RTK or through the GTP-binding protein, Ras. The signal is then transmitted to the nucleus and to other cytoplasmic proteins via MAPKK and MAPK.

Most protein serine-threonine kinases undergo autophosphorylation. The autophosphorylation of most protein kinases is associated with an increase in kinase activity [4, 10]. In some instances, such as with the RII subunit of PKA, autophosphorylation represents a positive feedback mechanism for kinase activation, in this case by enhancing the rate of dissociation of the RII and C subunits. In the case of CaMKII, autophosphorylation causes the catalytic activity of the enzyme to become independent of Ca2+ and calmodulin. This means that the enzyme, activated originally in response to elevated cellular Ca2+, remains active after Ca2+ concentrations have returned to baseline. By this mechanism, neurotransmitters that activate CaMKII can produce relatively long-lived alterations in neuronal function. In other instances, such as with the receptor-associated protein tyrosine kinases (discussed in Ch. 24), autophosphorylation is an obligatory step in the sequence of molecular events through which those kinases are activated and produce physiological effects. 

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