All Peptide Hormones After Cell Function by Phosphorylation, While Steroid Act by Altering Gene Expression - Essay Example

?All peptide hormones alter cell function by phosphorylation, while steroid hormones act by altering gene expression. Discuss. One of the principal characteristics of cells enabling them to sustain life is their ability to exchange signals or communicate. Communication at cellular level occurs both within as well as between the cells. Distant communication along blood vessels and nerve fibers is set up by the endocrine, immune and neuronal systems, while molecular and substructure interactions take place at the subcellular level. The signaling molecules in intercellular communication are called first messengers, which carryout various forms of signaling such as contact dependent, paracrine, synaptic, and endocrine signaling. For instance, endocrine signaling involves the secretion of specific hormonal signals in the blood stream which are then distributed to other parts of the body. The first messenger molecule cannot pass through the target cell membrane, but instead are bound by specific receptors. Intracellular communication takes place when receptors activate secondary messengers or signaling proteins which convey those signals through chemical reaction to the nucleus of the cell (Marks, 2008). Proteins are the key signal processors in a cell. The incredible structural flexibility and chemical reactivity offers characteristic signal transduction property i.e., signals movement inside from outside of the cell, to all proteins. The input signals allow conformational changes in the structure altering the specific protein functions and cellular activity. Proteins capable of binding to a phosphate molecule are called phospho-proteins, and play a central role in the signaling pathway regulating various cellular processes. Protein phosphorylation or phosphoregulation is a reversible process which regulates the protein function by covalent modification. To switch between phosphorylized and dephosphorylized states, specific kinase (tyrosine, serine/threonine) and phosphatase enzymes act respectively. Phosphorylation may either increase or decrease activity depending on specific type of enzyme. The affinity towards interacting cohort protein, enzymatic action, and subcellular localization and other functional changes are altered by protein phosphorylation (Goto, Kiyono and Inagaki, 2007). As a signaling molecule, proteins have a receiver and a transmitter module. In order to recognize and decode a specific signal, the receiver requires prior information for that signal which has to be either obtained or is genetically fixed. To coordinate signal and its exact implication, differentiation occurs exclusively in the receptor cells or target proteins. For instance, adrenaline hormonal signal has different meanings for different target tissues or target proteins control various functional consequences of phosphorylation. The intercellular signaling molecules including peptides, amino acids, amines and proteins cannot enter cell membrane and thus interact with receptors on the surface. The output signal transduction in receptor proteins results in a conformational alterations which are then differentiated by other signal transducing proteins along the pathway such as G-proteins. The chemical interactions taking place as a result of signal reception are not definite sequences, but rather diffused and complex excitation patterns (King, 2012). The hormones secreted by endocrine tissues get attached to particular plasma carrier proteins and composites are then distributed to distant parts. The receptors in the responding tissues have very high affinity for hormones and regulate metabolism of target through a coupled process. The receptors for amino acid and peptide hormones are mostly present on the cell membrane. Signal transducing receptors are classified into receptors with ability to enter cell membrane such as tyrosine kinases, tyrosine phosphatases and serine/threonine kinases, serpentine receptors which are coupled such as adrenergic and odorant receptors, and nuclear or intracellular receptors such as steroid and thyroid hormone receptors. Receptors are different in structure. Some of them are single polypeptide chain having a domain on both surfaces of the membrane, while others are arranged back and forth in a serpentine fashion transversely providing several domains. Some may also comprise more than one polypeptide chain (Liu and Pepper, 2011). Peptide hormones of the brain include hypothalamic peptide hormones and neuropeptides which perform functions of neurotransmitters, neurohormones, and neuromodulators. The pituitary function is influenced by hypothalamic peptide hormones, which in turn controls entire endocrine function of the body. The compounds produced by endocrine glands can thus perform neurotransmitterial as well as hormonal functions. The peptide neurotransmitters operate through signal transmission, the release being highly dependent upon Ca2+ ions. After a peptide hormone binds to its receptor, phosphorylated proteins and second messengers (such as cAMP, IP3, Ca2+, DAG) make specific metabolic responses to signal transduced from outside the cell. The hormone-binding signal in most cell membrane receptors is transmitted inside the cell by attachment of receptor complexes to sequence of other binding proteins known as the G-proteins (Nogrady and Weaver, 2005). The G-protein on G-protein coupled receptors (GPCRs) helps inactivation of adenylate cyclase. ATP is converted to cAMP by the action of Adenylate cyclase, and increase in cAMP levels activates cAMP dependent protein kinase (PKA). The GPCRs are also involved in activation of phospholipase C-? (PLC?). The IP3 and DAG levels are elevated due to hydrolyzation of membrane phospholipids by active PLC ?. Alterations in function through subsequent phosphorylation of donstream signaling proteins on serine and threonine by action of PKA and DAG-activated protein kinase C (PKC). Several intra-cellular tyrosine kinases also act to phosphorylate precise tyrosine residues on target proteins. The gonadotropin hormones secreted by the anterior pituitary such as ACTH, LH, FSH, hCG and hMG are released in a pulsed manner to perform their activities. For instance, the interaction of ACTH with receptors of different affinities causes differences between the extent of steroidogenesis and cAMP generation. The production of cAMP in turn mediates the primary effect of ACTH (King, 2012). Some peptide receptors such as epidermal growth factor receptor (EGFR) undergo autophosphorylation after binding, with aid of specific receptor kinases allowingrecognition and attachment of additional proteins. The signaling mechanism in insulin receptors is similar to EGFR, but instead of direct binding, the ligand induced receptor autophosphorylation provide the stimulus for attaching the bridging proteins known as insulin receptor substrate proteins. Some receptors such as growth hormone receptors induce a conformational change in receptor which allows binding of a second protein. The conformation change is usually triggered by receptor dimerization (Melmed and Conn, 2005). The thyroid hormone receptors are not present on membrane surface as these molecules are capable of penetrating the hydrophobic plasma membrane, thus locating their receptors in cytoplasm or the nucleus where they may attach to target DNA sequences leading to changes in transcription rates of the related gene. Thyroid stimulating hormone binding to its receptor activates a signaling cascade leading to increase in cAMP, PKA, IP3, and DAG. These messengers further increase the secretion of the thyroid hormones, T4 and T3. This mechanism also leads to enhanced hormone synthesis and thyroid cell growth. (Liu and Pepper, 2011; Garret and Grisham, 2005). Like thyroid hormones, receptors for the steroid hormones are also located in intracellular environment. Steroids are lipid soluble short peptides, and can pass extra-cellular membrane barrier, get activated through conformation as ligand binds, and move towards nuclear receptors for carrying out respective functions in gene transcription. This hormone category comprises sex hormones (androgens, estrogens, progestins), adrenocorticoids (glucocorticoids, mineralocorticoids), and cholesterol precursor. They consist of characteristic ligand-binding, DNA-binding and transcription regulatory domains, and binding of steroid hormones to nucleotide sequences directly alters the transcription levels (Wenlong and Nancy, 1995; Nogrady and Weaver, 2005). Upon diffusion into the cell as free steroids, these molecules bind to the ligand binding domain of receptor proteins forming a complex. The complex is then attached to chaperone peptides which contain heat shock proteins, and help in optimal binding of steroid to the receptor. Steroid receptors are large protein molecules, all consisting of macromolecules such as heat-shock proteins (such as hsp 70, hsp 90 etc.), and are classified as type I nuclear receptors. The dissociation of the complex results in release of chaperones activating the receptor complex. The active receptor undergoes phosphorylation, and is transported to the nucleus by support of the hinge section. The DNA binding domain then binds to the DNA, effectuating gene expression for protein synthesis. The optimal affinity of hormones for their receptors is vital in determining the duration for a synthetic response. For instance, estriol binds more weakly than estradiol, triggering a rapid response. Unlike the larger peptide hormones, steroid hormones thus act by either enhancing or suppressing gene expression in nucleus of the target cells (Nogrady and Weaver, 2005). References Garrett, R. and Grisham, C., 2005. Biochemistry. 3rd ed. Belmont CA: Thomson Brooks/Cole. Goto, H., Kiyono, T. and Inagaki, M., 2007. Functional analyses for site-specific phosphorylation of a target protein in cells. Protocol Exchange, Nature Publishing Group. [online] Available at: [Accessed 28 April 2012]. King, M. W., 2012. Peptide hormones. Themedicalbiochemistrypage.org, LLC. [online] Available at: < http://themedicalbiochemistrypage.org/peptide-hormones.php> [Accessed 28 April 2012]. Liu, J. Q. and Peper, F., 2011. Signal transduction in biological systems and its possible uses in computation and communication systems. In: H, Sawai, ed. 2011. Biological functions for information and communication technologies: Theory and inspiration. London: Springer. Marks, F., 2008., The brain of the cell. In: F. Marks, ed. 2008. Protein phosphorylation. New York: VCH. Melmed, S. and Conn, P. M., 2005.Endocrinology: Basic and clinical principles. 2nd ed. New Jersey: Humana Press. Nogrady, T. and Weaver, D. F., 2005. Medicinal chemistry: A molecular and biochemical approach. 3rd ed. New York: Oxford. Wenlong, B. and Nancy, L. W., 1995. Phosphorylation and steroid hormone action, In: G. Litwack, ed. 1995. Vitamins & Hormones, Academic Press, 51, 289-313. Read More